Haematological and Biochemical Changes in Response to Stress Induced by the Administration of Amikacin Injection by Autoinjector in Animals

The drugs administered by autoinjectors, may act fast reducing the morbidity and mortality in critical and emergency situations. Amikacin drug cartridge was developed for the autoinjector as an antibacterial drug for critical situations and its tolerability was studied. Rats were given either 3 doses or 7 doses on consecutive days by the autoinjector (intraperitoneal, 63 mg/mL). Blood was withdrawn on the 4th day (3 doses) or the 8th day (7 doses), and haematological and biochemical parameters were studied. All the parameters studied were within the limits and did not show any significant difference when compared with the control. Rabbits were given 3 doses of two concentrations (intramuscular, 63 or 250 mg/mL) and on the 4th day blood was withdrawn for the haematological and biochemical estimations. 63 mg/mL cartridge did not show any significant change while 250 mg/mL cartridge showed significant change in the haematological and biochemical parameters. This study showed that intraperitoneal injection of amikacin by the autoinjector designed for intramuscular injection was well tolerated by the rats. In the rabbits, low dose (63 mg/mL) was tolerated while the higher dose, which is an adult human dose (250 mg/mL) showed significant changes.Defence Science Journal, 2014, 64(2), pp. 99-105. DOI: http://dx.doi.org/10.14429/dsj.64.503

Urine levels of rifampicin & isoniazid in asymptomatic HIV-positive individuals

Background & objectives: AIDS and its associated gastrointestinal complications may impair the absorption of anti-tuberculosis (TB) drugs. Impaired absorption of anti-TB drugs could lead to low drug exposure, which might contribute to acquired drug resistance and reduced effectiveness of anti-TB treatment. The aim of this study was to obtain information on the status of absorption of rifampicin (RMP) and isoniazid (INH) in asymptomatic HIV- positive individuals, who are less immunocompromised. The D-xylose absorption test was also carried out to assess the absorptive capacity of intestive. Methods: The absorption of RMP, INH and D-xylose was studied in 15 asymptomatic HIV- positive individuals with CD4 cell counts > 350 cells/mm3 and 16 healthy volunteers, after oral administration of single doses of RMP (450 mg), INH (300 mg) and D-xylose (5 g). Urine was collected up to 8 h after drug administration. Percentage dose of the drugs and their metabolites and D-xylose excreted in urine were calculated. Results: A significant reduction in the urinary excretion of INH and D-xylose in HIV-positive persons compared to healthy volunteers was observed. The per cent dose of RMP and its metabolite, desacetyl RMP was also lower in HIV-positive persons compared to healthy volunteers, but this difference was not statistically significant. Interpretation & conclusion: Decreased urinary excretion of D-xylose and INH are suggestive of intestinal malabsorption in HIV-positive individuals. HIV infection could cause malabsorption of anti-TB drugs even at an early stage of the disease. The clinical implications of these findings need to be confirmed in larger studies

Pharmacophore modeling and 3D-QSAR studies on substituted benzothiazole / benzimidazole analogues as DHFR inhibitors with antimycobacterial activity

ABSTRACT The resurgence of tuberculosis and the emergence of multidrug-resistant strains of Mycobacteria drugs has propelled the development of new structural classes of antitubercular agents. The present study was undertaken to investigate the opportunities which the enzyme dihydrofolate reductase, a promising drug target for treatment of Mycobacterial infections offers for the development of new TB drugs. Pharmacophore models were established by using the HipHop and HypoGen algorithms implemented in the Catalyst software package. The best quantitative pharmacophore model, consisted of two hydrogen bond acceptor, a hydrophobic aliphatic, and a ring aromatic feature which has the highest correlation coefficient (0.93), as well as enrichment factor of 1.75 and Goodness of hit score of 0.73. Based on the pharmacophore model some leads were optimized and some of its derivatives were synthesized and analysed by following QSAR studies. About 25 compounds of substituted benzothiazole/ benzimidazole derivatives were synthesized as potent DHFR inhibitors and screened for antimycobacterial activity. To further explore the structure-activity relationships of all newly synthesized compounds, 3D-QSAR analyses were developed. MFA studies were performed with the QSAR module of Cerius2 using genetic partial least squares (G/PLS) algorithm. The predictive ability of the developed model was assessed using a training set of 25 and a test set of 5 compounds (r2pred = 0.924).The analyzed MFA model demonstrated a good fit, having r2 value of 0.868 and cross validated coefficient r2cv value of 0.771

Single dose pharmacokinetics of lamivudine in healthy volunteers: comparison of blood and urine kinetics

Aims: To study single dose pharmacokinetics of lamivudine (3TC) in healthy subjects. Methods: Twelve healthy subjects were administered 3TC (150 mg) followed by timed blood and urine collections up to 24 hours. Pharmacokinetic variables and percent dose of 3TC in urine were calculated. Results: Plasma exposure and percent dose of 3TC in urine were highly correlated (p < 0.001; r = 0.96). 3TC concentration at 24 hours was undetectable in all study subjects. Conclusions: Timed urine measurements could be used to study bioavailabilty of 3TC. Plasma 3TC measurements could be used to monitor adherence among HIV-infected patients on antiretroviral treatment.Aims: To study single dose pharmacokinetics of lamivudine (3TC) in healthy subjects. Methods: Twelve healthy subjects were administered 3TC (150 mg) followed by timed blood and urine collections up to 24 hours. Pharmacokinetic variables and percent dose of 3TC in urine were calculated. Results: Plasma exposure and percent dose of 3TC in urine were highly correlated (p < 0.001; r = 0.96). 3TC concentration at 24 hours was undetectable in all study subjects. Conclusions: Timed urine measurements could be used to study bioavailabilty of 3TC. Plasma 3TC measurements could be used to monitor adherence among HIV-infected patients on antiretroviral treatment

Effect of rifampicin & isoniazid on the steady state pharmacokinetics of moxifloxacin.

BACKGROUND & OBJECTIVES Moxifloxacin (MFX) is reported to have promising antimycobacterial activity, and has a potential to shorten tuberculosis (TB) treatment. We undertook this study to examine the influence of rifampicin (RMP) and isoniazid (INH) on the steady state pharmacokinetics of MFX individually in healthy individuals. METHODS A baseline pharmacokinetic study of MFX (400 mg once daily) was conducted in 36 healthy adults and repeated after one week of daily MFX with either RMP (450/600 mg) (n = 18) or INH (300 mg) (n = 18). Plasma MFX concentrations were determined by a validated HPLC method. RESULTS Plasma peak concentration and exposure of MFX was significantly lower and plasma clearance significantly higher when combined with RMP (P<0.001). The C max to MIC and AUC 0-12 to MIC ratios of MFX were significantly lower during concomitant RMP (P<0.001). INH had no significant effect on the pharmacokinetics of MFX. INTERPRETATION & CONCLUSIONS Concomitant RMP administration caused a significant decrease in C max and AUC 0-12 of MFX, the mean decreases being 26 and 29 per cent, respectively. It is uncertain whether this decrease would affect the treatment efficacy of MFX. Prospective studies in TB patients are needed to correlate MFX pharmacokinetics with treatment outcomes

Daisy Chella et.al Indian Journal of Research in Pharmacy and Biotechnology ISSN: 2321-5674(Print) ISSN: 2320 – 3471(Online) Formulation and characterization of Methotrexate loaded sodium alginate chitosan

The aim of the present work was to formulate nanoparticles for Methotrexate drug. Methotrexate is an anticancer, disease modifying anti rheumatic drug, and BCS Class – III drug having high solubility and low permeability. Nanoparticles were prepared by ionotropic pregelation method using Box Behnen Formula. The concentration of chitosan (X1),concentration of sodium alginate (X2) and concentration of Methotrexate (X3) were chosen as independent variables while particle size, drug entrapment efficiency and percentage drug release at 36 th hour, was taken as dependent variables. The dissolution profile of selected formulations was fitted to zero order, first order, Higuchi and Korsemayer Peppas models to ascertain the kinetic modeling of drug release. The prepared formulations were further evaluated for characterization like surface morphology, particle size distribution, zetapotential and drug excipient interaction study by Fourier Transformer Infra Red Spectroscopy, Differential Scanning Calorimetry and X-ray Diffraction. All independent variables were found to significantly influence the particle size, entrapment efficiency and percentage of drug release. The in- vitro drug release profile showed that the suitability of sodium alginate-chitosan loaded nanoparticles in controlled release of methotrexate for prolonged time

Urine levels of rifampicin &#38; isoniazid in asymptomatic HIV-positive individuals

Background &#38; Objective: AIDS and its associated gastrointestinal complications may impair the absorption of anti-tuberculosis (TB) drugs. Impaired absorption of anti-TB drugs could lead to low drug exposure, which might contribute to acquired drug resistance and reduced effectiveness of anti-TB treatment. The aim of this study was to obtain information on the status of absorption of rifampicin (RMP) and isoniazid (INH) in asymptomatic HIV- positive individuals, who are less immunocompromised. The D-xylose absorption test was also carried out to assess the absorptive capacity of intestive. Methods: The absorption of RMP, INH and D-xylose was studied in 15 asymptomatic HIV-positive individuals with CD4 cell counts>350 cells/mm3 and 16 healthy volunteers, after oral administration of single doses of RMP (450 mg), INH (300 mg) and D-xylose (5 g). Urine was collected up to 8 h after drug administration. Percentage dose of the drugs and their metabolites and D-xylose excreted in urine were calculated. Results: A significant reduction in the urinary excretion of INH and D-xylose in HIV-positive persons compared to healthy volunteers was observed. The per cent dose of RMP and its metabolite, desacetyl RMP was also lower in HIV-positive persons compared to healthy volunteers, but this difference was not statistically significant. Interpretation &#38; Conclusion: Decreased urinary excretion of D-xylose and INH are suggestive of intestinal malabsorption in HIV-positive individuals. HIV infection could cause malabsorption of anti-TB drugs even at an early stage of the disease. The clinical implications of these findings need to be confirmed in larger studies