Assessment of potential interaction between simvastatin and clarithromycin in healthy adult male subjects

Cardiac patients with weak immune system are susceptible to bacterial infections. Their prescriptions frequently contain simvastatin and clarithromycin together. The objective of present project was to assess the potential interaction between simvastatin and clarithromycin by evaluating the clarithromycin effects on the pharmacokinetics of simvastatin in healthy adult male subjects. The study design comprised of two phases, used at interval of one week. In first phase simvastatin 20 mg alone was administered to each volunteer. In second phase, co-administration of simvastatin 20 mg with clarithromycin 250 mg was made under similar specified conditions. Blood samples were collected at specified time intervals. Simvastatin plasma concentrations were analyzed through High Performance Liquid Chromatography with UV detector at 238 nm wavelength. Using one compartment open model, MW/PHARM version 3.02 software program was used by F. Rombut for pharmacokinetic parameters calculation. Clarithromycin co-treatment resulted in 2.3 fold increase in maximum plasma concentration Cmax [from 2.47 +/- 0.34 ng.mL-1 to 5.66 +/- 1.18 ng.mL-1; p<0.05] and 3.9 fold increase in area under time versus concentration curve from 0 to 10 hours AUC0-10 [from 15.10 +/- 3.73 ng.hr.mL-1 to 58.49 +/- 15.73 ng.hr.mL-1; p<0.05] of simvastatin. These results suggest that co-prescription of simvastatin and clarithromycin should be avoided to minimize the adverse events resulting from high simvastatin concentration, without sacrificing therapeutic worth of simvastatin

Pharmacokinetic behavior of montelukast in indigenous healthy male volunteers

Aim of present study was to investigate the pharmacokinetic behavior of Montelukast in the healthy male volunteers under indigenous conditions. One tablet of montelukast 10 mg was administered in each subject and blood at different time intervals. Concentration of montelukast in plasma samples was analyzed by high performance liquid chromatography method to calculate pharmacokinetic parameters. The plasma concentration of montelukast was in the range of 1.31-1.76 micro g/mL at 0.5-12 hours with C[max] value of 1.59+/-0.16 micro g/mL at 3.71+/-0.64 hours. These values of plasma drug concentrations were above the minimum effective concentration of montelukast during the entire study hours. Absorption and elimination half-lives of the montelukast were evaluated as 2.52+/-0.54 hours and 2.63+/-0.35 hours, respectively. The volume of distribution and total body clearance of montelukast were investigated as 0.34+/-0.01 L/kg and 0.01+/-0.00 L/hr/kg, respectively. The pharmacokinetic parameters i.e. Cmax, AUC, t1/2, Vd and ClB of montelukast calculated in present study were found different as compared to that of the previous literature values which was due to genetic and environmental variation