Gabapentin Bioequivalence Study: Quantification By Liquid Chromatography Coupled To Mass Spectrometry

The study was performed to compare the bioavailability of two gabapentin 400 mg capsule formulation (Gabapentin from Arrow Farmacêutica S/A as test formulation and Neurontin ® from Pfizer, Brazil, as reference formulation) in 26 volunteers of both sexes. The study was conducted open with randomized two period crossover design and a one week wash out period. Plasma samples were obtained over a 48 hour interval. The gabapentin was analyzed by LC/MS/MS, in the presence of pracetamole as internal standard. With plasma concentration vs. time curves, data obtained from this metabolite, the following pharmacokinetics parameters were obtained: AUC 0-t, AUC 0-inf and C max. Geometric mean of gabapentin/Neurontin ® 400 mg individual percent ratio was 100.58% AUC 0-t, 101.35% for AUC 0-inf and 97.76% for C max. The 90% confidence intervals were 92.00 - 109.95%, 93.00 - 110.44%, 88.41 - 108.10%, respectively. Since the 90% confidence intervals for C max, AUC 0-t and AUC 0 -inf were within the 80 - 125% interval proposed by Food and Drug Administration, it was concluded that gabapentin 400 mg capsule was bioequivalent to Neurontin ® 400 mg capsule according to both the rate and extent of absorption. © 2011 Junior EA, et al.38187190Wattananat, T., Akarawut, W., Validated LC-MS-MS Method for the Determination of Gabapentin in Human Plasma: Application to a Bioequivalence Study (2009) J Chromatogr Sci, 47, pp. 868-871Stewart, B.H., Kagler, A.R., Thompson, P.R., Bockbrader, H.N., A saturable transport mechanism in the intestinal absorption of gabapentin is the underlying cause of the lack of proportionality between increasing dose and drug levels in plasma (1993) Pharma Res, 10, pp. 276-281McLean, M.J., Gabapentin in the management of convulsive disorders (1999) Epilepsia, 40, pp. 39-50Goa, K.L., Sorkin, E.M., Gabapentin: A review of its pharmacological properties and clinical potential in epilepsy (1993) Drugs, 46, pp. 409-427Zhu, Z., Neirinck, L., High-performance liquid chromatographic method for the determination of gabapentin in human plasma (2002) J Chromatogr B Analyt Technol Biomed Life Sci, 779, pp. 307-312Sagirli, O., Cetin, S.M., Determination of gabapentin in human plasma and urine by high-performance liquid chromatography with UV-vis detection (2006) J Pharm Biomed Anal, 42, pp. 618-624Jalalizadeh, H., Souri, E., Tehrani, M.B., Jahangiri, A., Validated HPLC method for the determination of gabapentin in human plasma using precolumn derivatization with 1-fluoro-2,4-dinitrobenzene and its application to a pharmacokinetic study (2007) J Chromatogr B Analyt Technol Biomed Life Sci, 854, pp. 43-47Forrest, G., Sills, G.J., Leach, J.P., Brodie, M.J., Determination of gabapentin in plasma by high-performance liquid chromatography (1996) J Chromatogr B Analyt Technol Biomed Life Sci, 681, pp. 421-425Tang, P.H., Miles, M.V., Glauser, T.A., Degrauw, T., Automated microanalysis of gabapentin in human serum by high-performance liquid chromatography with fluorometric detection (1999) J Chromatogr B Analyt Technol Biomed Life Sci, 727, pp. 125-129Hassan, E.M., Belal, F., Al-Deeb, O.A., Khalil, N.Y., Spectrofluorimetric determination of vigabatrin and gabapentin in dosage forms and spiked plasma samples through derivatization with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (2001) J. AOAC Int., 84, pp. 1017-1024Gauthier, D., Gupta, R., Determination of gabapentin in plasma by liquid chromatography with fluorescence detection after solid-phase extraction with a C18 column (2002) Clin Chem, 48, pp. 2259-2261Chung, T.C., Tai, C.T., Wu, H.L., Simple and sensitive liquid chromatographic method with fluorimetric detection for the analysis of gabapentin in human plasma (2006) J Chromatogr A, 119, pp. 294-298Bahrami, G., Kiani, A., Sensitive high-performance liquid chromatographic quantitation of gabapentin in human serum using liquid-liquid extraction and pre-column derivatization with 9-fluorenylmethyl chloroformate (2006) J Chromatogr B Analyt Technol Biomed Life Sci, 835, pp. 123-126Krivanek, P., Koppatz, K., Turnheim, K., Simultaneous isocratic HPLC determination of vigabatrin and gabapentin in human plasma by dansyl derivatization (2003) Ther Drug Monit, 25, pp. 374-377Chang, S.Y., Wang, F.Y., Simple and sensitive liquid chromatographic method with fluorimetric detection for the analysis of gabapentin in human plasma (2004) J Chromatogr B Analyt Technol Biomed Life Sci, 799, pp. 265-270Wolf, C.E., Saady, J.J., Poklis, A., Determination of gabapentin in serum using solid phase extraction and gas-liquid chromatography (1996) J Anal Toxicol, 20, pp. 498-501Kushnir, M.M., Cossett, J., Brown, P.I., Urry, F.M., Analysis of gabapentin in serum and plasma by solid-phase extraction and gas chromatography-mass spectrometry for therapeutic drug monitoring (1999) J Anal Toxicol, 23, pp. 1-6Borrey, D.C., Godderis, K.O., Engelrelst, V.I., Bernard, D.R., Langlois, M.R., Quantitative determination of vigabatrin and gabapentin in human serum by gas chromatography-mass spectrometry (2005) Clin Chim Acta, 354, pp. 147-151Gambelunghe, C., Mariucci, G., Tantucci, M., Ambrosini, M.V., Gas chromatography-tandemmass spectrometry analysis of gabapentin in serum (2005) Biomed Chromatogr, 19, pp. 63-67Matar, K.M., Abdel-Hamid, M.E., Rapid tandem mass spectrometric method for determination of gabapentin in human plasma (2005) Chromatographia, 61, pp. 499-504Ramakrishna, N.V.S., Vishwottam, K.N., Koteshwara, M., Maroj, S., Santosh, M., Rapid quantification of gabapentin in human plasma by liquid chromatography/tandemmass spectrometry (2006) J Pharm Biomed Anal, 40, pp. 360-368Ifa, D.R., Falci, M., Moraes, M.E., Bezerra, F.A., Moraes, M.O., Gabapentin quantification in human plasma by high-performance liquid chromatography coupled to electrospray tandem mass spectrometry. Application to bioequivalence study (2001) J Mass Spectrom, 36, pp. 188-194Ji, H.Y., Jeong, D.W., Kim, Y.H., Kim, H.H., Yoon, Y.S., Determination of gabapentin in human plasma using hydrophilic interaction liquid chromatography with tandem mass spectrometry (2006) Rapid Commun Mass Spectrom, 20, pp. 2127-2132Carlsson, K.C., Reubsaet, J.L., Sample preparation and determination of gabapentin in venous and capillary blood using liquid chromatography-tandem mass spectrometry (2004) J Pharm Biomed Anal, 34, pp. 415-423Park, J.H., Jhee, O.H., Park, S.H., Lee, J.S., Lee, M.H., Validated LC-MS/ MS method for quantification of gabapentin in human plasma: Application to pharmacokinetic and bioequivalence studies in Korean volunteers (2007) Biomed Chromatogr, 21, pp. 829-83

Comparative Bioavailability Of Two Quetiapine Formulations In Healthy Volunteers After A Single Dose Administration

The study was performed to compare the bioavailability of two quetiapine 25 mg tablet formulations: the test formulation was quetiapine fumarate (kitapen®) manufactured by Cobalt Pharmaceuticals, Canada/ Arrow Farmacêutica Ltda* (Erowlabs). Seroquel® (quetiapine) from Astrazeneca Brazil was used as reference formulation. The study was conducted open with randomized two period crossover design and one week wash out period in 64 volunteers of both sexes. Plasma samples were obtained over a 48 hour interval. Quetiapine was analyzed by LC-MS-MS in the presence of quetiapine-D8 as internal standard. Plasma samples were obtained over a 48 hour interval. Quetiapine was analyzed by LC-MS-MS in the presence of quetiapine-D8 as internal standard. The mean ratio of parameters Cmax and AUC 0-t and 90% confidence intervals of correspondents were calculated to determine the bioequivalence. The means AUC 0-t for test and reference formulation were 432.41 ng.h/mL and 412.20 ng.h/mL, for AUC 0-∞ were 440.06 ng.h/mL and 418.90 ng.h/mL and, for Cmax 126.94 ng/mL and 108.71 ng/mL, respectively. Geometric mean of quetiapine (kitapen®)/Seroquel® 25 mg individual percent ratio was 97.68% AUC 0-t, 97.47% for AUC 0-∞ and 90.68% for C max. The 90% confidence intervals were 92.67 - 102.96%, 92.53 - 102.67%, 83.37 - 98.64%, respectively. Since the 90% confidence intervals for C max, AUC 0-t and AUC 0-∞ were within the 80 - 125% interval proposed by Food and Drug Administration, it was concluded that quetiapine (kitapen®) 25 mg tablet was bioequivalent to Seroquel® 25 mg tablet according to both the rate and extent of absorption. © 2011 Junior EA, et al.38178181Barrett, B., Capek, H.M., Huclova, J., Borek-Dohalsky, V., Fejt, P., Validated HPLC-MS/MS method for determination of quetiapine in human plasma (2007) Journal of Pharmaceutical and Biomedical Analysis, 44, pp. 498-505DeVane, C.L., Nemeroff, C.B., Clinical Pharmacokinetics of quetiapine: An Atypical Antipsychotic (2001) Clinical Pharmacokinet, 40, pp. 509-522Kasper, S., Müller-Spahn, F., Review of quetiapine and its clinical applications in schizophrenia (2000) Expert Opin Pharmacother, 1, pp. 783-801Tilden, D., Aristides, M., Meddis, D., Burns, T., An economic assessment of quetiapine and haloperidol in patients with schizophrenia only partially responsive to conventional antipsychotics (2002) Clin Ther., 24, pp. 1648-1667Mario, A., Michael, E., The Role of Quetiapine Extended Release in the Treatment of Bipolar Depression (2010) Adv Ther, 27, pp. 1-11Keck, P., McIntyre, R., Shelton, R., Bipolar depression: Best practices for the outpatient (2007) CNS Spectr., 12, pp. 1-16Judd, L., Akishal, H., Schettler, P., The long-term natural history of the weekly symptomatic status of bipolar I disorder (2002) Arch Gen Psychiatry., 59, pp. 530-537Goldstein, J.M., Atypical antipsychotic drugs: Beyond acute psychosis, new directions (1999) Emerging Drugs, 4, pp. 127-151Abi-Dargham, A., Laruelle, M., Aghajanian, G.K., Charney, D., Krystal, J., The role of serotonin in the pathophysiology and treatment of schizophrenia (1997) J Neuropsychiatry Clin Neurosci, 9, pp. 1-17Kapur, S., Remington, G., Serotonin-dopamine interaction and its relevance to schizophrenia (1996) Am J Psychiatry, 153, pp. 466-476Calabrese, J.R., Keck Jr., P.E., McFadden, W., Minkwitz, M., Ketter, T.A., Weisler, R.H., Cutler, A.J., Mullen, J., A randomized, doubleblind, placebo-controlled trial of quetiapine in the treatment of bipolar I or II depression (2005) Am J Psychiatry, 162, pp. 1351-1360Copolov, D.L., Kowalcyk, B., A multicentre, double-blind, randomized comparison of quetiapine and haloperidol in schizophrenia (2000) Psychol Med, 30, pp. 95-105Figueroa, C., Brecher, M., Hamer-Maansson, J., Pharmacokinetic profiles of extended release quetiapine fumarate compared with quetiapine immediate release (2009) Prog Neuropsychopharmacol Biol Psychiatry, 33, pp. 199-204Goldstein, J.M., Litwin, L.C., Sutton, E.B., Malick, J.B., Seroquel: Electrophysiological profile of a potential atypical antipsychotic (1993) Psychopharmacology, 112, pp. 293-298Kasper, S., Tauscher, J., Küfferle, B., Barnas, C., Pezawas, L., Dopamine and serotonin-receptors in schizophrenia: Results of imaging-studies and implications for pharmacology in schizophrenia (1999) Eur. Arch. Psychiatry Clin. Neurosci., 249, pp. 83-89Peuskens, J., A comparison of quetiapine and chlorpromazine in the treatment of schizophrenia (1997) Acta Psychiatr Scand, 96, pp. 265-273Saller, F., Salama, A.I., Seroquel: Biochemical profile of a potential atypical antipsychotic (1993) Psychopharmacology, 112, pp. 285-292Thase, M.E., McFadden, W., Weisler, R., Efficacy of quetiapine monotherapy in bipolar I and II depression: A double-blind, placebo-controlled study (2006) J Clin Psychopharmacol, 26, pp. 600-609Vieta, E., Mullen, J., Brecher, M., Paulsson, B., Jones, M., Quetiapine monotherapy for mania associated with bipolar disorder: Combined analysis of two international, double-blind, randomised, placebo-controlled studies (2005) Curr Med Res Opin, 21, pp. 923-93

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Comparative Bioavailability: Two Pramipexole Formulations In Healthy Volunteers After A Single Dose Administration Under Fasting Conditions

The study was performed to compare the bioavailability of two Pramipexole 0.125 mg tablet formulations: the test formulation was pramipezan® (pramipexole) manufactured by Cobalt Pharmaceuticals, Canada/ Arrow Farmacêutica Ltda*. Sifrol® (Pramipexole) from Boehringer Ingelheim do Brasil Química e Farmacêutica Ltda was used as reference formulation. The study was conducted open with randomized two period crossover design and 8 days wash out period in 48 volunteers of both sexes. Plasma samples were obtained over a 48 hour interval. Pramipexole was analyzed by LC-MS-MS in the presence of Tansulosina as internal standard. The mean ratio of parameters C max. and AUC 0-t and 90% confidence intervals of correspondents were calculated to determine the bioequivalence. The means AUC 0-t for test and reference formulation were 8201.90 pg.h/mL and 7891.56 pg.h/mL, for AUC 0-∞ were 8574.71 pg.h/mL and 8288.01 pg.h/mL and, for C max 642.09 pg/mL and 633.94 pg/mL, respectively. Geometric mean of pramipezan® (pramipexole) /Sifrol® 0.125 mg individual percent ratio was 103.61% AUC 0-t, 103.13% for AUC 0-∞ and 100.81% for C max. The 90% confidence intervals were 98.02 - 109.51%, 97.95 - 108.59%, 93.06 - 109.21%, respectively. Since the 90% confidence intervals for C max' AUC 0-t and AUC 0-∞ were within the 80 - 125% interval proposed by Food and Drug Administration, it was concluded that Pramipezan®(pramipexole) 0.125 mg tablet was bioequivalent to Sifrol®0.125 mg tablet according to both the rate and extent of absorption. © 2012 Abib E Jr, et al.455659Hughes, A.J., Daniel, S.E., Blankson, S., Lees, A.J., A clinicopathologic study of 100 cases of Parkinson's disease (1993) Arch Neurol, 50, pp. 140-148Eriksen, J.L., Wszolek, Z., Petrucelli, L., Molecular pathogenesis of Parkinson disease (2005) Arch Neurol, 62, pp. 353-357Samii, A., Nutt, J.G., Ransom, B.R., Parkinson's disease (2004) Lancet, 363, pp. 1783-1793Lesage, S., Brice, A., Parkinson's disease: From monogenic forms to genetic susceptibility factors (2009) Hum Mol Genet, 18, pp. 48-59Piercey, M.F., Pharmacology of pramipexole, a dopamine D3-preferring agonist useful in treating Parkinson's disease (1998) Clin Neuropharmacol, 21, pp. 141-151Gottwald, M.D., Bainbridge, J.L., Dowling, G.A., Aminoff, M.J., Alldredge, B.K., New pharmacotherapy for Parkinson's disease (1997) Ann Pharmacother, 31, pp. 1205-1217Lange, K.W., Clinical pharmacology of dopamine agonists in Parkinson's disease (1998) Drugs Aging, 13, pp. 381-389Lang, A.E., Lozano, A.M., Parkinson's disease. First of two parts (1998) N Engl J Med, 339, pp. 1044-1053Lang, A.E., Lozano, A.M., Parkinson's disease. Second of two parts (1998) N Engl J Med, 339, pp. 1130-1143Schapira, A.H.V., Science, medicine, and the future: Parkinson's disease (1999) BMJ, 318, pp. 311-314Grosset, K.A., Bone, I., Grosset, D.G., Suboptimal medication adherence in Parkinson's disease (2005) Mov Disord, 20, pp. 1502-1507Moller, J.C., Oertel, W.H., Pramipexole in the treatment of Parkinson's disease: New developments (2005) Expert Rev Neurother, 5, pp. 581-586Pinter, M.M., Pogarell, O., Oertel, W.H., Efficacy, safety, and tolerance of the non-ergoline dopamine agonist pramipexole in the treatment of advanced Parkinson's disease: A double blind, placebo controlled, randomised, multicentre study (1999) J Neurol Neurosurg Psychiatry, 66, pp. 436-441Shannon, K.M., Bennett Jr., J.P., Friedman, J.H., Efficacy of pramipexole, a novel dopamine agonist, as monotherapy in mild to moderate Parkinson's disease. The Pramipexole Study Group (1997) Neurology, 49, pp. 724-728Safety and efficacy of pramipexole in early Parkinson disease. A randomized dose-ranging study (1997) JAMA, 278, pp. 125-130. , AnonymousHubble, J.P., Koller, W.C., Cutler, N.R., Sramek, J.J., Friedman, J., Pramipexole in patients with early Parkinson's disease (1995) Clin Neuropharmacol, 18, pp. 338-347Hubble, J.P., Pre-clinical studies of pramipexole: Clinical relevance (2000) Eur J Neurol, 7, pp. 15-20Rascol, O., Brooks, D.J., Korczyn, A.D., de Deyn, P.P., Clarke, C.E., A five-year study of the incidence of dyskinesia in patients with early Parkinson's disease who were treated with ropinirole or levodopa (2000) N Engl J Med, 342, pp. 1484-1491Nilsson, D., Hansson, L.E., Johansson, K., Nystrom, C., Paalzow, L., Long-term intraduodenal infusion of a water based levodopa-carbidopa dispersion in very advanced Parkinson's disease (1998) Acta Neurol Scand, 97, pp. 175-183Stocchi, F., Vacca, L., Ruggieri, S., Olanow, C.W., Intermittent vs continuous levodopa administration in patients with advanced Parkinson disease: A clinical and pharmacokinetic study (2005) Arch Neurol, 62, pp. 905-910Debattista, C., Solvason, H.B., Breen, J.A., Schatzberg, A.F., Pramipexole augmentation of a selective serotonin reuptake inhibitor in the treatment of depression (2000) J Clin Psychopharmacol, 20, pp. 274-27

Standardizing Selection Criteria In Nasal Medication Studies [padronização Dos Critérios De Seleção Em Estudos Sobre Medicações Nasais]

Clinical studies on nasal topical medications require the standardization of "nasosinusal normality" in order to establish control groups through a specific evaluation of the upper airways. Aim: to standardize the evaluation of candidates for control groups in clinical studies on nasal topical medications. Material and Methods: healthy male volunteers of 18 to 50 years of age, asymptomatic from the nasosinusal standpoint were subjected to a sequential and excluding assessment made up of clinical evaluation, immediate hypersensitivity skin test, saccharin test, flexible nasofibroscopy and nasal cytology. Study design: Crosssectional contemporary cohort. Results: Of the 33 people originally enrolled, 14 (42.4%) were excluded for clinical reasons. Of the 19 remaining, 2 (10.5%) had atopy diagnosed in the skin test and were excluded. 17 were tested with saccharin and presented normal mucociliary clearance. Evaluation by nasal endoscopy showed abnormality in 2 cases (11.8%) and these were excluded. The remaining 15 were submitted to nasal cytology, which proved normal, representing 45.5% of those initially included. Conclusion: The proposed protocol for sequential and excluding evaluation was effective in defining candidates for the establishment of control groups in clinical studies on nasal topical medications. © Revista Brasileira de Otorrinolaringologia. All Rights reserved.756Santos, U.P., Rumel, D., Martarello, N.A., Ferreira, C.S.W., Matos, M.P., Síndrome dos edifícios doentes em bancários. (1992) Rev Saúde Publ SP, 26 (6), pp. 400-404Polosa, R., Ciamarra, I., Mangano, G., Prosperi, G., Pistorio, M.P., Vancheri, C., Bronchial hyperresponsiveness and airway inflammation markers in nonasthmatics with allergic rhinitis (2000) Eur Respir J, 15 (1), pp. 30-35Wiikmann, C., Chung, D., Lorenzetti, F., Lessa, M., Voegles, R., Butugan, O., Comparação entre solução salina fisiológica e a hipertônica tamponada após cirurgia endoscópica nasossinusal. (2002) Arq Otorrinolaringol, 6 (2), pp. 186-190Homer, J.J., Dowley, A.C., Condon, L., El-Jassar, P., Sood, S., The effect of hypertonicity on nasal mucociliary clearance (2000) Clin Otolaryngol Allied Sci, 25 (6), pp. 558-560Moreno, P., Trindade, R.P., Avaliação da formação de crostas pósturbinectomia em pacientes em uso de solução salina a 4,5 mg/g em gel. RBM-ORL (2007), 3, pp. 100-101Schwetz, S., Olze, H., Melchisedech, S., Grigorov, A., Latza, R., Efficacy of pollen blocker cream in the treatment of allergic rhinitis (2004) Arch Otolaryngol Head Neck Surg, 130, pp. 979-984Ercan, I., Cakir, B.O., Ozcelik, M., Turgut, S., Efficacy of tonimer gel spray on postoperative nasal care after endonasal surgery (2007) ORL J Otorhinolaryngol Relat Spec, 69 (4), pp. 203-206Unal, M., Görür, K., Ozcan, C., Ringer-lactate solution versus isotonic saline solution on mucociliary function after nasal septal surgery (2001) J Laryngol Otol, 115 (10), pp. 796-797Demarco, R.C., Anselmo-Lima, W.T., Fisiologia do nariz e seios paranasais (2002) Campos, CahCosta, Hoo. Tratado de Otorrinolaringologia, 50, pp. 627-639. , São Paulo: Roca, CapLousana G, Accetturi C. Histórico da Pesuisa Clínica. In Pesquisa Clínica no Brasil - Greyce Lousana org. Revinter, Rio de Janeiro, RJ 2002 (ISBN 85-7309-632-2) cap 1, p 1Caruso, S., Serra, A., Grillo, C., Maiolono, L., Agnello, A., Di Mari, L., Characteristics of nasal epithelial cells in naturally postmenopausal women receiving hormone therapy with 1 mg 17b-estradiol and 2 mg drospirenone: A prospective study (2008) Menopause, 15 (5), pp. 1-4Rocha, F.M.N., (2005) Relação da poluição atmosférica com citologia nasal em pacientes com rinite alérgica, , Tese de Doutorado da Faculdade de Medicina da Universidade de São Paulo Departamento de Oftalmologia e Otorrinolaringologia, São PauloCorbo, G.M., Foresi, A., Bonfitto, P., Mugnano, A., Agabiti, N., Cole, P.J., Measurement of nasal mucociliary clearance (1989) Arch Dis Child, 64, pp. 546-550Stanley, P., MacWilliam, L., Greenstone, I.A., Cole, P., Efficacy of a saccharin test for screening to detect abnormal mucociliary clearance (1984) Br J Chest, 78, pp. 62-65Grassel, S.S., Alves, V.A.F., Silva, C.S., Cruz, O.L.M., Almeida, E.R., Oliveira, E., Clinical and histopathological changes of the nasal mucosa induced by occupational exposure to sulphuric acid mists (2003) Occup Environ Med, 60, pp. 395-402Glück, U., Schütz, R., Gebbers, J.-O., Cytopathology of the nasal mucosa in chronic exposure to diesel engine emission: A five-year survey of swiss customs officers (2003) Env Helth Perspec, 111 (7), pp. 925-929Jacobson, M.R., Juliussun, S., Lowhagen, O., Balder, B., Kay, A.B., Durham, S.R., Effect of topical corticosteroids on seasonal increases in epithelial eosinophils and mast cells in allergic rhinitis: A comparison of nasal brush and biopsy methods (1999) Clin Exp Allergy, 29 (10), pp. 1347-1355Maru, Y.K., Munjal, S., Gupta, Y., Brush cytology and its comparison with histopathological examination in cases of disease of the nose (1999) J Laryngol Otol, 113 (11), pp. 983-987Rizzo, J.A., Medeiros, D., Silva, A.R., Sarinho, E., Benzalkoonium chloride and nasal mucociliary clearance: A randomized, placebo-controlled, crossover, double-blind trial (2006) Am J Rhinol, 20 (3), pp. 243-247Puchelle, E., Aug, F., Pham, Q.T., Bertrand, A., Comparison of three methods for measuring nasal mucociliary clearance in man (1981) Acta Otolaryngol, 91, pp. 297-303Kennedy, D.W., Loury, M.C., Nasal and sinus pain: Current diagnosis and treatment (1988) Semin Neurol, 8 (4), pp. 303-314Lerner AP, Castro FFM, Santos MA. 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Study Of Relative Bioavailability/bioequivalence Of Two Formulations Of Risendronate Sodium In Healthy Volunteers Of Both Sexes [estudo De Biodisponibilidade Relativa/bioequivalência De Duas Formulações De Risedronato De Sódio Em Voluntários Sadios De Ambos Os Sexos]

The study was conducted to compare the bioavailability of two formulations of Risedronate Sodium 35 mg tablet (risedronate sodium of Aché S/A test formulation and Actonel® from Sanofi-Aventis Pharmaceuticals Inc. reference formulation, Brazil) in 80 volunteers both sexes. This was an open, randomized, two-sequence, two-period, crossover single dose two treatments, in which a group of volunteers received the test formulation and the other reference formulation. Blood samples were obtained throughout a 96 hours interval. The risedronate sodium concentrations were determined by mass spectrometry (UPLC-MS-MS) using risedronic acid-D4 (deuterated risedronate) as internal standard. From the data obtained, calculate the following pharmacokinetic parameters: AUC 0-t, AUC 0-∞ and Cmax. The geometric mean of risedronate sodium /Actonel ® 35 mg were 101.90% for AUCO-t, 97.95% for AUC 0-∞ and 100.70% for Cmax. The 90% confidence intervals were 86.43%-120.14%, 83.04%-115.54% and 85.50%-118.61%, respectively. Since the confidence intervals 90% for Cmax and AUC0-t was within the range 80%-125% proposed by the FDA and ANVISA (National Agency of Sanitary Surveillance in Brazil), it is concluded that the tablet of sodium risedronate 35 mg was bioequivalent to Actonel ® tablet of 35 mg and thus the test product may be considered interchangeable in medical practice. © Copyright Moreira Jr. Editora. Todos os direitos reservados.698-9225229Souza, P.M., Diagnóstico e tratamento da osteoporose (2010) Rev Bras Ortop, 45, pp. 220-229Chesnut, C.H., Treatment of postmenopausal osteoporosis (1984) Compr Ther, 10, pp. 14-17Marshall, D., Johnell, O., Wedel, H., Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures (1996) British Medical Journal, 312 (7041), pp. 1254-1259Szejnfeld, V.L., Osteoporosis (2004) Revista Brasileira de Medicina, 61 (7), pp. 417-428Nordin, B.C., Chatterton, B.E., Need, A., Horowitz, M., The definition, diagnosis and classification of osteoporosis (1997) Phys Med Rehabil Clin North Am, 6, pp. 395-414Whedon, G.D., Osteoporosis (1987) N Engl J Med, 6, pp. 397-398Brewer, V., Meyer, B.M., Keele, M.S., Role of exercise in prevention of involutional bone loss (1983) Medicine and Science in Sports and Exercise, 15 (6), pp. 445-449Cimaz, R., Biphosphonates in pediatric rheumatic diseases (2003) Pediatric Rheumatology on Line Journal, 1, pp. 134-139Licata, A.A., Bisphosphonate therapy (1997) American Journal of the Medical Sciences, 313 (1), pp. 17-22. , DOI 10.1097/00000441-199701000-00004Fleisch, H.A., Bisphosphonates: Preclinical aspects and use in osteoporosis (1997) Annals of Medicine, 29 (1), pp. 55-62Weinstein, R.S., Roberson, P.K., Manolagas, S.C., Giant osteoclast formation and long-term oral bisphosphonate therapy (2009) N Engl J Med, 360, pp. 53-62Brookler, K., Medical treatment of otosclerosis: Rationale for use of bisphosphonates (2008) Int Tinnitus J, 14, pp. 92-96Heikkinen, J.E., Selander, K.S., Laitinen, K., Arnala, I., Vaananen, H.K., Short-term intravenous bisphosphonates in prevention of postmenopausal bone loss (1997) Journal of Bone and Mineral Research, 12 (1), pp. 103-110. , DOI 10.1359/jbmr.1997.12.1.103Warner, C., (2011) Risedronato de Sódio Comprimidos: Informações de Prescrição, , Rockaway, NJMcClung, M.R., Geusens, P., Miller, P.D., Zippel, H., Bensen, W.G., Roux, C., Adami, S., Chestnut III, C.H., Effect of risedronate on the risk of hip fracture in elderly women (2001) New England Journal of Medicine, 344 (5), pp. 333-340. , DOI 10.1056/NEJM200102013440503Russell, R.G.G., Rogers, M.J., Bisphosphonates: From the laboratory to the clinic and back again (1999) Bone, 25 (1), pp. 97-106. , DOI 10.1016/S8756-3282(99)00116-7, PII S875632829900116

A Replicated Study Of Relative Bioavailability Of Two Formulations Of Sodium Ibandronate In Healthy Female (postmenopausal And Non-menopausal) And Male Volunteers [estudo Replicado De Biodisponibilidade Relativa De Duas Formulações De Ibandronato De Sódio Em Voluntários Sadios Dos Sexos Feminino (pós-menopausa E Não Menopausa) E Masculino]

The study was conducted to compare the bioavailability of two formulations of ibandronate sodium 150 mg tablets (ibandronate sodium of Aché S/A testing and formulation of Bonviva® Roche Products Chemicals and Pharmaceuticals S.A. reference formulation, Brazil) in 80 volunteers of both sexes (20 female volunteers in post-menopausal, 20 volunteers sex femino not in menopause and 40 male volunteers). This was an open, replicated, randomized, two-sequence, four-period, crossover in two treatments, in which a group of volunteers received the test formulation and the other reference formulation. Plasma samples were obtained throughout a 72 hours interval. The concentrations of sodium ibandronate were determined by mass spectrometry (UPLC-MS-MS) using deuterated ibandronate as internal standard. From the data obtained, calculate the following pharmacokinetic parameters: AUC 0-t, AUC 0-∞ and Cmax. The geometric mean of ibandronate sodium / Bonviva® 150 mg individual percent ratio were 102.18% for AUC 0-t, 102.14% for AUC 0-∞, and 100.64% for Cmax. The 90% confidence intervals were 94, 89-110.03%, 94.92-109.91%, 91.88-110.23%, respectively. Since the confidence intervals 90% for Cmax and AUC 0-t was within the range 80-125% proposed by the FDA and ANVISA (National Agency of Sanitary Surveillance in Brazil), it is concluded that the tablet of sodium Thandronate 150 mg was bioequivalent to Bonviva® tablet of 150 mg and thus the test product may be considered interchangeable in medical practice. © Copyright Moreira Jr. Editora.695-6119123Souza, P.M., Diagnóstico e tratamento da osteoporose (2010) Rev Bras Ortop, 45, pp. 220-229Marshall, D., Johnell, O., Wedel, H., Meta-analysis of how well measures of bone mineral density predict occurrence of osteoporotic fractures (1996) British Medical Journal, 312 (7041), pp. 1254-1259Szejnfeld, V.L., Osteoporosis (2004) Revista Brasileira de Medicina, 61 (7), pp. 417-428Cimaz, R., Biphosphonates in pediatric rheumatic diseases (2003) Pediatric Rheumatology on Line Journal, 1, pp. 134-139Licata, A.A., Bisphosphonate therapy (1997) American Journal of the Medical Sciences, 313 (1), pp. 17-22. , DOI 10.1097/00000441-199701000-00004Fleisch, H.A., Bisphosphonates: Preclinical aspects and use in osteoporosis (1997) Annals of Medicine, 29 (1), pp. 55-62Weinstein, R.S., Roberson, P.K., Manolagas, S.C., Giant osteoclast formation and long-term oral bisphosphonate therapy (2009) N Engl J Med, 360, pp. 53-62Brookler, K., Medical treatment of otosclerosis: Rationale for use of bisphosphonates (2008) Int Tinnitus J, 14, pp. 92-96Meunier, P.J., Confavreux, E., Tupinon, I., Hardouin, C., Delmas, P.D., Balena, R., Prevention of early postmenopausal bone loss with cyclical etidronate therapy (a double-blind, placebo-controlled study and 1-year follow-up) (1997) Journal of Clinical Endocrinology and Metabolism, 82 (9), pp. 2784-2791. , DOI 10.1210/jc.82.9.2784Pouilles, J.M., Tremollieres, F., Roux, C., Sebert, J.L., Alexandre, C., Goldberg, D., Treves, R., Kuntz, D., Effects of cyclical etidronate therapy on bone loss in early postmenopausal women who are not undergoing hormonal replacement therapy (1997) Osteoporosis International, 7 (3), pp. 213-218. , DOI 10.1007/BF01622291Herd, R.J.M., Balena, R., Blake, G.M., Ryan, P.J., Fogelman, I., The prevention of early postmenopausal bone loss by cyclical etidronate therapy: A 2-year, double-blind, placebo-controlled study (1997) American Journal of Medicine, 103 (2), pp. 92-99. , DOI 10.1016/S0002-9343(97)00019-3, PII S0002934397000193Wimalawansa, S.J., Combined therapy with estrogen and etidronate has an additive effect on bone mineral density in the hip and vertebrae: Four-year randomized study (1995) Am J Med, 99, pp. 36-42Ravn, P., Clemmesen, B., Riis, B.J., Christiansen, C., The effect on bone mass and bone markers of different doses of ibandronate: A new bisphosphonate for prevention and treatment of postmenopausal osteoporosis (1996) Bone, 19, pp. 527-1233Heikkinen, J.E., Selander, K.S., Laitinen, K., Arnala, I., Vaananen, H.K., Short-term intravenous bisphosphonates in prevention of postmenopausal bone loss (1997) Journal of Bone and Mineral Research, 12 (1), pp. 103-110. , DOI 10.1359/jbmr.1997.12.1.103Adachi, J.D., Bensen, W.G., Brown, J., Hanley, D., Hodsman, A., Josse, R., Kendler, D.L., Pack, S., Intermittent etidronate therapy to prevent corticosteroid-induced osteoporosis (1997) New England Journal of Medicine, 337 (6), pp. 382-387. , DOI 10.1056/NEJM199708073370603Roux, C., Oriente, P., Laan, R., Hughes, R.A., Ittner, J., Goemaere, S., Di, M.O., Cortet, B., Randomized trial of effect of cyclical etidronate in the prevention of corticosteroid-induced bone loss (1998) Journal of Clinical Endocrinology and Metabolism, 83 (4), pp. 1128-1133. , DOI 10.1210/jc.83.4.1128Geusens, P., Dequeker, J., Vanhoof, J., Stalmans, R., Boonen, S., Joly, J., Nijs, J., Raus, J., Cyclical etidronate increases bone density in the spine and hip of postmenopausal women receiving long term corticosteroid treatment. A double blind, randomised placebo controlled study (1998) Annals of the Rheumatic Diseases, 57 (12), pp. 724-727Pitt, P., Li, F., Todd, P., Webber, D., Pack, S., Moniz, C., A double blind placebo controlled study to determine the effects of intermittent cyclical etidronate on bone mineral density in patients on long term oral corticosteroid treatment (1998) Thorax, 53 (5), pp. 351-356Struys, A., Snelder, A.A., Mulder, H., Cyclical etidronate reverses bone loss of the spine and proximal femur in patients with established corticosteroid-induced osteoporosis (1995) Am J Med, 99, pp. 235-242Heilberg, I.P., Martini, L.A., Teixeira, S.H., Szejnfeld, V.L., Carvalho, A.B., Lobao, R., Draibe, S.A., Effect of etidronate treatment on bone mass of male nephrolithiasis patients with idiopathic hypercalciuria and osteopenia (1998) Nephron, 79 (4), pp. 430-437. , DOI 10.1159/000045089Anderson, F.H., Francis, R.M., Bishop, J.C., Rawlings, D.J., Effect of intermittent cyclical disodium etidronate therapy on bone mineral density in men with vertebral fractures (1997) Age and Ageing, 26 (5), pp. 359-365. , DOI 10.1093/ageing/26.5.359Harris, S.T., Watts, N.B., Jackson, R.D., Genant, H.K., Wasnich, R.D., Ross, P., Miller, P.D., Chesnut III, C.H., Four-year study of intermittent cyclic etidronate treatment of postmenopausal osteoporosis: Three years of blinded therapy followed by one year of open therapy (1993) American Journal of Medicine, 95 (6), pp. 557-567. , DOI 10.1016/0002-9343(93)90350-XMiller, P.D., Watts, N.B., Licata, A.A., Harris, S.T., Genant, H.K., Wasnich, R.D., Ross, P.D., Chesnut III, C.H., Cyclical etidronate in the treatment of postmenopausal osteoporosis: Efficacy and safety after seven years of treatment (1997) American Journal of Medicine, 103 (6), pp. 468-476. , DOI 10.1016/S0002-9343(97)00278-7, PII S0002934397002787Van Staa, T.P., Abenhaim, L., Cooper, C., Use of cyclical etidronate and prevention of non-vertebral fractures (1998) BrJ Rheumatol, 37, pp. 87-94Storm, T., Steiniche, T., Thamsborg, G., Melsen, F., Changes in bone histomorphometry after long-term treatment with intermittent, cyclic etidronate for postmenopausal osteoporosis (1993) Journal of Bone and Mineral Research, 8 (2), pp. 199-208Barrett, J., Worth, E., Bauss, F., Epstein, S., Ibandronate: A clinical pharmacological and pharmacokinetic update (2004) Journal of Clinical Pharmacology, 44 (9), pp. 951-965. , DOI 10.1177/0091270004267594Pillai, G., Gieschke, R., Goggin, T., Barrett, J., Worth, E., Steimer, J.-L., Population pharmacokinetics of ibandronate in Caucasian and Japanese healthy males and postmenopausal females (2006) International Journal of Clinical Pharmacology and Therapeutics, 44 (12), pp. 655-667Ravn, P., Neugebauer, G., Christiansen, C., Association between pharmacokinetics of oral ibandronate and clinical response in bone mass and bone turnover in women with postmenopausal osteoporosis (2002) Bone, 30 (1), pp. 320-324. , DOI 10.1016/S8756-3282(01)00665-2, PII S8756328201006652Papapoulos, S.E., Ibandronate: A potent new bisphosphonate in the management of postmenopausal osteoporosis (2003) International Journal of Clinical Practice, 57 (5), pp. 417-422Russell, R.G.G., Rogers, M.J., Bisphosphonates: From the laboratory to the clinic and back again (1999) Bone, 25 (1), pp. 97-106. , DOI 10.1016/S8756-3282(99)00116-7, PII S8756328299001167Russo, T.A.L., Osteoporose pos-menopausa: Opções terapêuticas (2001) Arq Bras Endocrinol Metab, 45, pp. 401-40

Study Of Relative Bioavailability/bioequivalence Of Two Formulations Of Rosuvastatin Calcium In Healthy Volunteers For Both Sexes [estudo De Biodisponibilidade Relativa/bioequivalência De Duas Formulações De Rosuvastatina Cálcica Em Voluntários Sadios De Ambos Os Sexos]

The study was conducted to compare the bioavailability of two formulations of rosuvastatin calcium 20 mg tablet (rosuvastatin calcium of Aché S/A test formulation and Crestor® from AstraZeneca do Brasil Ltda. reference formulation, Brazil) in 24 volunteers both sexes. This was an open, randomized, two-sequence, two-period, crossover single dose two treatments, in which a group of volunteers received the test formulation and the other reference formulation. Blood samples were obtained throughout a 96 hours interval. The rosuvastatin calcium concentrations were determined by mass spectrometry (UPLC-MS-MS) using atorvastatin as internal standard. From the data obtained, calculate the following pharmacokinetic parameters: AUC 0-t, AUC 0-∞ and Cmax. The geometric mean of rosuvastatin calcium/Crestor® 20 mg were 93,97% for AUC 0-t, 97,43% for AUC 0-∞ and 93,63% for Cmax. The 90% confidence intervals were 82,26-107,34%, 85,82-110,61% and 81,58-107,45%, respectively. Since the confidence intervals 90% for Cmax and AUC 0-t was within the range 80-125% proposed by the FDA and ANVISA (National Agency of Sanitary Surveillance in Brazil), it is concluded that the tablet of rosuvastatin calcium 20 mg was bioequivalent to Crestor® tablet of 20 mg and thus the test product may be considered interchangeable in medical practice. © Copyright Moreira Jr. Editora.697167172Moghadasian, M.H., Experimental atherosclerosis: A historical overview (2002) Life Sci, 70, pp. 855-865Kritchevsky, D., Dietary protein, cholesterol and atherosclerosis: A review of the early history (1995) J Nutr, 125, pp. 587-593Lichtman, A.H., Clinton, S.K., Iyama, K., Connelly, P.W., Libby, P., Cybulsky, M.I., Hyperlipidemia and atherosclerotic lesion development in LDL receptor deficient mice fed defined semipurified diets with and without cholate (1999) Arterioscler Thromb Vasc Biol, 19, pp. 1938-1944Melo, F.S., Toledo, J.C.Y., Coca, A.P., Junior, H.M., Hipertensão arterial, aterosclerose e inflamação: O endotélio como órgäo-alvo (2007) Rev Bras Hipertens, 14, pp. 234-238Michael, P., Christopher, P., Use of lipid lowering drugs for primary prevention of coronary heart disease: Meta-analysis of randomised trials (2000) BMJ, 321, p. 983Forti, N., Diament, J., Efeitos indesejáveis dos hipolipemiantes: Condutas na prática clínica (2008) Rev Assoc Med Bras, 54 (357), p. 362Davignon, J., Beneficial cardiovascular pleiotropic effects of statins (2004) Circulation, 109, pp. 39-43Wassmann, S., Laufs, U., Baumer, A.T., HMG-CoA reductase inhibitors improve endothelial dysfunction in normocholesterolemic hypertension via reduced production of reactive oxygen species (2001) Hypertension, 37, pp. 1450-1457Kwak, B., Mulhaupt, F., Myit, S., Mach, F., Statins as a newly recognized type of immunomodulator (2000) Nature Medicine, 6, pp. 1399-1402Mason, J.C., Statins and their role in vascular protection (2003) Clinical Science, 105, pp. 251-266Masato, E., Kozai, T., Cosentino, F., Statin prevents tissue factor expression in human endothelial cells. Role of Rho/Rho-kinase and AKT pathways (2002) Circulation, 105, pp. 1756-1759Ichiki, T., Takeda, K., Todunou, T., Down regulation of angiotensin II type 1 receptor by hydrophobic 3-hydroxy-3-methylglutaryl coenzima A reductase inhibitors in vascular smooth muscle cells (2001) Arterioscl Thromb Vasc Biol, 21, pp. 1896-1901Walter, D.H., Rittig, K., Bahlmann, F.H., Statin therapy acelerates reendothelization: A novel effect involving mobilization and incorporation of bone marrow-derived endothelial progenitor cells (2002) Circulation, 105, pp. 3017-3024Harper, C.R., Jacobson, T.A., The broad spectrum of statin myopathy: From myalgia to rhabdomyolysis. Hyperlipidaemia and cardiovascular disease (2007) Current Opinion in Lipidology, 18, pp. 401-408Taggart, F., Buckett, L., Davidson, R., Holdgate, G., McCormick, A., Schneck, D., Preclinical and clinical pharmacology of rosuvastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A reducatase inhibitor (2001) Am J Cardiol, 87, pp. 28-32Buckett, L., Ballard, P., Davidson, R., Dunkley, C., Martin, L., Stafford, J., Selectivity of ZD4522 for inhibition of cholesterol synthesis in hepatic versu non-hepatic cells (2000) Atherosclerosis Supplements, 141, p. 151Brown, C.D.A., Windass, A., Bleasby, A., Lauffart, B., Rosuvastatin is a high affinity substrate of hepatic organic anion transporter OATP-C (2001) Atherosclerosis Supplements, 2, p. 90Smith, G., Davidson, R., Bloor, S., Burns, K., Calnam, C.C., Aulay, P.M.C., Pharmacological properties of ZD4522 - A new HMG-CoA reductase inhibitor (2000) Atherosclerosis Supplements, 139, p. 151Schuster, H., Rosuvastatin-a highly effective new 3-hydroxy-3-methylglutaryl Coenzyme. A reductase inhibitor: Review of clinical trial data at 10-40 mg doses in dyslipidemic patients (2003) Cardiology, 99, pp. 126-139Jones, P.H., Davidson, M.H., Stein, E.A., Bays, H.E., Mckenney, J.M., Miller, E., Comparison of efficacy and safety of rosuvastatin versus atorvastatin. Simvastatin, and pravastatin across doses (2003) Am J Cardiol, 92, pp. 152-160Chapman, M.J., Taggart, F., Optimizing the pharmacology of statins: Characteristics of rosuvastatin (2002) Atherosclerosis Supplements, 2, pp. 33-36Cooper, K.J., Martin, P.D., Dane, A.L., Warwick, M.J., Raza, A., Schneck, D.W., Lack of effect of ketoconazole on the pharmacokinetics of rosuvastatin in healthy subjects (2003) Br J Clin Pharmacol, 55, pp. 94-99Schneck, D.W., Knopp, R.H., Ballantyne, C.M., McPherson, R., Chitra, R.R., Simonson, S.G., Comparative effects of rosuvastatin and atorvastatin across their dose ranges in patients with hypercholesterolemia and without active arterial disease (2003) Am J Cardiol, 91, pp. 33-41Blasetto, J.W., Stein, E.A., Brown, W.V., Chitra, R., Raza, A., Efficacy of rosuvastatin compared with other statins at selected starting doses in hypercholesterolemia patients and in special population groups (2003) Am J Cardiol, 91, pp. 3-10Shepherd, J., Hunninghake, D.B., Barter, P., McKenney, J.M., Hutchinson, H.G., Guidelines for lowering lipids to reduce coronary artery disease risk: A comparison of rosuvastatin with atorvastatin, pravastatin, and simvastatin for achieving lipid lowering goals (2003) Am J Cardiol, 91, pp. 11-19Davidson, M., Ma, P., Stein, E.A., Gotto, A.M., Raza, J.A., Chitra, R., Comparison of effects on low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with rosuvastatin versus atorvastatin in patients with type IIa or Iib hypercholesterolemia (2002) Am J Cardiol, 89, pp. 268-275Ballantyne, C.M., Stein, E.A., Paoletti, R., Southworth, H., Blasetto, J.W., Efficacy of rosuvastatin 10mg in patients with the metabolic syndrome (2003) Am J Cardiol, 91, pp. 25-28Moghadasian, M.H., Mancini, G.B.J., Frohlich, J.J., Pharmacotherapy of hyperchcholesterolaemia: Statins in clinical practice (2000) Exp Opin Pharmacother, 1, pp. 683-695Rader, D.J., Davidson, M.H., Caplan, R.J., Pears, J.S., Lipid and apolipoprotein ratios:association with coronary artery disease and effects of rosuvastatin compared with atorvastatin, pravastatin and simvastatin (2003) Am J Cardiol, 91, pp. 20-24Istvan, E.S., Deisenhofer, J., Structural Mechanism for statin inhibition of HMG-CoA reductase (2001) Science, 292, pp. 1160-1164Oliveira, C.M., Dislipidemias (2011) RBM. Rev. Bras. Med., 68, pp. 42-60Cheung, B.M.Y., Lauder, I.J., Lau, C., Rumana, C.R., Meta-analysis of large randomized controlled trials to evaluate the impact of statins on cardiovascular outcomes (2004) Br J Clin Pharmacol, 57, pp. 640-651Cheng-Lai, A., Rosuvastatin: A new HMG-CoA reductase inhibitor for the treatment of hypercholesterolemia (2003) Heart Disease, 5, pp. 72-78Kemp, J., Martin, P., Olive, M.D., Coadministration of rosuvastatin does not alter the pharmacokinetics of digoxin (2001) Pharmacotherapy, 21, p. 1255Coelho, V.G., Perfil lipídico e fatores de risco para doenças cardiovasculares em estudantes de medicina (2005) Arq Bras Cardiol, 85, pp. 57-6