Farmacocinetica populacional de cafeina em recem nascidos prematuros

Significant differences are seen between pediatric and adult populations in what concerns drug disposition processes when both groups are submitted to identical pharmacotherapy regimen. Despite the recent advances on pediatric clinical pharmacology, one can state that logistical and ethical difficulties arose, since always, to the investigation within this kind of population. The obtention of results and scientifically valid conclusions is difficult enough to enable someone to surname pediatrics as an "therapeutic orphan group". Neonatal apnea is a common problem occurring is 25% of newborns with a birth weight #<=#2.5 kg and 84% of those born with #<=#1Kg. In spite of this known situation, the information on the utilization of caffeine for this therapeutic purpose in the pediatric population is rather insufficient. The aim of the present study was to characterize the kinetic profile of caffeine in a premature newborn population through the development of a mixed effects model implemented with the NONMEM program (Nonlinear Mixed Effects Model), a computer software developed for population al analysis, exclusively using information obtained from the routine clinical care. The optimization of posological regimens, according to the specificity of patients, relies on the obtention of a final pharmacostatistic model that takes into consideration the influence of several physiological maturation indexes and special characteristics of treatment on the kinetic performance of caffeine. Once established the viability of the used methodology to perform the determination of population pharmacokinetic parameters from retrospective data, free from ethical limitations, we demonstrated the influence of some variables like the body weight, postnatal age, parenteral nutrition and low gestational age (#<=#28 weeks) on the kinetic profile of our population. Since now, the caffeine utilization of caffeine is possible to be done more accurately owing to the inclusion on the structural model of physiological maturation indexes that make possible the elaboration of dynamic dosing schedules more closely related with patients characteristicsAvailable from Fundacao para a Ciencia e a Tecnologia, Servico de Informacao e Documentacao, Av. D. Carlos I, 126, 1200 Lisboa / FCT - Fundação para o Ciência e a TecnologiaSIGLEPTPortuga

A physiological approach to renal clearance:From premature neonates to adults

Aims: We propose using glomerular filtration rate (GFR) as the physiological basis for distinguishing components of renal clearance. Methods: Gentamicin, amikacin and vancomycin are thought to be predominantly excreted by the kidneys. A mixed-effects joint model of the pharmacokinetics of these drugs was developed, with a wide dispersion of weight, age and serum creatinine. A dataset created from 18 sources resulted in 27,338 drug concentrations from 9,901 patients. Body size and composition, maturation and renal function were used to describe differences in drug clearance and volume of distribution. Results: This study demonstrates that GFR is a predictor of two distinct components of renal elimination clearance: (1) GFR clearance associated with normal GFR and (2) non-GFR clearance not associated with normal GFR. All three drugs had GFR clearance estimated as a drug-specific percentage of normal GFR (gentamicin 39%, amikacin 90% and vancomycin 57%). The total clearance (sum of GFR and non-GFR clearance), standardized to 70 kg total body mass, 176 cm, male, renal function 1, was 5.58 L/h (95% confidence interval [CI] 5.50-5.69) (gentamicin), 7.77 L/h (95% CI 7.26-8.19) (amikacin) and 4.70 L/h (95% CI 4.61-4.80) (vancomycin). Conclusions: GFR provides a physiological basis for renal drug elimination. It has been used to distinguish two elimination components. This physiological approach has been applied to describe clearance and volume of distribution from premature neonates to elderly adults with a wide dispersion of size, body composition and renal function. Dose individualization has been implemented using target concentration intervention.</p

Efficacy and safety of eslicarbazepine acetate as add-on treatment in patients with focal-onset seizures: Integrated analysis of pooled data from double-blind phase III clinical studies

Purpose: To evaluate the efficacy and safety profile of eslicarbazepine acetate (ESL) added to stable antiepileptic therapy in adults with partial-onset seizures. Methods: Data from 1,049 patients enrolled from 125 centers, in 23 countries, in three phase III double-blind, randomized, placebo-controlled studies were pooled and analyzed. Following a 2-week titration period, ESL was administered at 400 mg, 800 mg, and 1,200 mg once-daily doses for 12 weeks. Key Findings: Seizure frequency was significantly reduced with ESL 800 mg (p 10% patients) were dizziness, somnolence, and headache. the incidence of AEs in ESL groups compared to placebo was generally consistent among different subpopulations. Significance: Once-daily ESL 800 mg and 1,200 mg showed consistent results across all efficacy and safety end points. Results were independent of study population characteristics and type and number of concomitant AEDs.BIAL - Portela Co, SABIALHosp Ruber Int, Dept Neurol, Madrid, SpainUniv Bonn, Dept Epileptol, Bonn, GermanySahlgrens Univ Hosp, Dept Clin Neurosci & Physiol, S-41345 Gothenburg, SwedenExpt Med Res Inst, Budapest, HungaryUniv Porto, Hosp Santo Antonio, Porto Hosp Ctr, Dept Cent Nervous Syst & Senses Organs, P-4100 Oporto, PortugalUniv Porto, Abel Salazar Biomed Sci Inst, P-4100 Oporto, PortugalUniversidade Federal de São Paulo, Paulista Med Sch, Neurol Studies Ctr, São Paulo, BrazilBIAL Portela & Ca SA, Dept Res & Dev, S Mamede Do Coronado, Portugal4Health Ltd, Cantanhede, PortugalUniv Coimbra, Fac Pharm, Coimbra, PortugalUniv Aveiro, Hlth Sci Sect, P-3800 Aveiro, PortugalUniv Porto, Fac Med, Dept Pharmacol & Therapeut, P-4100 Oporto, PortugalUniversidade Federal de São Paulo, Paulista Med Sch, Neurol Studies Ctr, São Paulo, BrazilWeb of Scienc

Treatment with subcutaneous and transdermal fentanyl : results from a population pharmacokinetic study in cancer patients

Transdermal fentanyl is effective for the treatment of moderate to severe cancer-related pain but is unsuitable for fast titration. In this setting, continuous subcutaneous fentanyl may be used. As data on the pharmacokinetics of continuous subcutaneous fentanyl are lacking, we studied the pharmacokinetics of subcutaneous and transdermal fentanyl. Furthermore, we evaluated rotations from the subcutaneous to the transdermal route. Fifty-two patients treated with subcutaneous and/or transdermal fentanyl for moderate to severe cancer-related pain participated. A population pharmacokinetic model was developed and evaluated using non-linear mixed-effects modelling. For rotations from subcutaneous to transdermal fentanyl, a 1:1 dose conversion ratio was used while the subcutaneous infusion was continued for 12 h (with a 50 % tapering after 6 h). A 6-h scheme with 50 % tapering after 3 h was simulated using the final model. A one-compartment model with first-order elimination and separate first-order absorption processes for each route adequately described the data. The estimated apparent clearance of fentanyl was 49.6 L/h; the absorption rate constant for subcutaneous and transdermal fentanyl was 0.0358 and 0.0135 h(-1), respectively. Moderate to large inter-individual and inter-occasion variability was found. Around rotation from subcutaneous to transdermal fentanyl, measured and simulated plasma fentanyl concentrations rose and increasing side effects were observed. We describe the pharmacokinetics of subcutaneous and transdermal fentanyl in one patient cohort and report several findings that are relevant for clinical practice. Further research is warranted to study the optimal scheme for rotations from the subcutaneous to the transdermal route

Evaluation of the main active species involved in the TiO2 photocatalytic degradation of ametryn herbicide and its by-products

In this study, we investigated the effectiveness of photocatalysis using TiO2 as catalyst on the removal of ametryn. The evaluation of photocatalytic activity under simulated sunlight was discussed as evidence by numerous controlled trials and several operational parameters such as ametryn concentration, total organic carbon, chemical oxygen demand, specific UV absorbance, biochemical oxygen demand, toxicity and formed intermediates. Moreover, the roles of reactive species involved in the degradation of ametryn were examined by using different specific scavengers. Ametryn removed by photocatalysis using 0.4 g L−1 of TiO2 was 100% within 60 min, while only 30% was achieved by photolysis at the same time. Biodegradability index improved from 0.3 (raw solution) up to 0.8 while the acute toxicity measured by the inhibition percentage of bioluminescence from Vibro fischeri indicates that the photocatalytic treatment promotes 97% of toxicity reduction. The scavenger study shows different percentages of inhibition in ametryn degradation, which allowed to conclude that HO¿, valence-band holes and O2¿− could intervene in the degradation of ametryn, with predominance of HO¿. Thirty-eight intermediates were identified from the photocatalytic degradation of ametryn. The comparison of the generation of those intermediates with and without the addition of scavengers showed that different by-products are generated depending on the predominance of the active species. For example, the presence of azide resulted in intermediates formed by condensation reactions. Based on the identified intermediates, reaction pathways and a degradation mechanism were proposed, including HO¿ radicals, O2¿−, holes, and 1O2