Comparative bioavailability of two brands of atenolol 100 mg tablets (Tensotin and Tenormin) in healthy human volunteers.

A bioequivalence study of two oral formulations of 100 mg atenolol was carried out in 24 healthy volunteers following a single dose, two-sequence, cross-over randomized design at the International Pharmaceutical Research Centre (IPRC), as a joint venture with Al-Mowasah Hospital, Amman, Jordan. The two formulations were Tensotin (Julphar, UAE) as test and Tenormin (Zeneca, UK) as reference product. Both test and reference tablets were administered with 240 ml of water to each subject after an overnight fast on 2 treatment days separated by a 1 week washout period. After dosing, serial blood samples were collected for a period of 36 h. Whole blood was analysed for atenolol by a sensitive, reproducible and accurate HPLC method with fluorescence detection capable of detecting atenolol in the range of 20-1600 ng/ml with a limit of quantitation of 20 ng/ml. Various pharmacokinetic parameters including AUC0-t, AUC0-proportional to), Cmax, Tmax, T1/2 and lambdaZ were determined from blood concentrations of both formulations and found to be in good agreement with reported values. AUC0-t, AUC0-proportional to), and Cmax were tested for bioequivalence after log-transformation of data using ANOVA and 90% confidence interval and were found within the acceptable range of 80%-125%. Based on these statistical inferences, it was concluded that Tensotin is bioequivalent to Tenormin.

Bioequivalence evaluation of two brands of enalapril 20 mg tablets (Narapril and Renitec) in healthy human volunteers.

The bioequivalence of two brands of enalapril 20 mg tablets was demonstrated in 24 healthy human volunteers after a single oral dose in a randomized cross-over study, conducted at IPRC, Amman, Jordan. Reference (Renitec, MSD, Netherlands) and test (Narapril, Julphar, UAE) products were administered to fasted male volunteers; blood samples were collected at specified time intervals, plasma separated and analysed for enalapril and its active metabolite (enalaprilat) using a validated LC-MS/MS method at Cartesius Analytical Unit, Institute of Biomedical Sciences, USP, Sao Paulo, Brazil. The pharmacokinetic parameters AUC(0-t), AUC(0-infinity), Cmax, Tmax, T(1/2) and elimination rate constant were determined from plasma concentration-time profile for both formulations and were compared statistically to evaluate bioequivalence between the two brands, using the statistical modules recommended by FDA. The analysis of variance (ANOVA) did not show any significant difference between the two formulations and 90% confidence intervals fell within the acceptable range for bioequivalence. Based on these statistical inferences it was concluded that the two brands exhibited comparable pharmacokinetic profiles and that Julphar's Narapril is bioequivalent to Renitec of MSD, Netherlands.

Pharmacokinetics and bioequivalence evaluation of two simvastatin 40 mg tablets (Simvast and Zocor) in healthy human volunteers.

The pharmacokinetics of two brands of simvastatin 40 mg tablets were compared in 24 healthy human volunteers after a single oral dose in a randomized cross-over study, conducted at IPRC, Amman, Jordan. Reference (Zocor, MSD, Netherlands) and test (Simvast, Julphar, UAE) products were administered to fasted volunteers; blood samples were collected at specified time intervals, plasma separated and analyzed for simvastatin and its active metabolite (beta-hydoxy acid) using a validated LC-MS/MS method at Cartesius Analytical Unit, Institute of Biomedical Sciences - USP, Sao Paulo, Brazil. The pharmacokinetic parameters AUC(0-t), AUC(0-variant), C(MAX), T(MAX), T(1/2) and elimination rate constant were determined from plasma concentration-time profile for both formulations and were compared statistically to evaluate bioequivalence between the two brands, using the statistical modules recommended by FDA. The analysis of variance (ANOVA) did not show any significant difference between the two formulations and 90% confidence intervals fell within the acceptable range for bioequivalence. Based on these statistical inferences it was concluded that the two brands exhibited comparable pharmacokinetic profiles and that Julphar's Simvast is bioequivalent to Zocor of MSD, Netherlands.

Comparison of two cyclosporine formulations in healthy Middle Eastern volunteers: bioequivalence of the new Sigmasporin Microoral and Sandimmun Neoral.

A study was conducted to establish bioequivalence between two oral cyclosporine 100 mg capsules, Sigmasporin Microoral (Gulf Pharmaceutical Industries - Julphar, United Arab Emirates, under technical co-operation with Sigma Pharma, Brazil) and Sandimmun Neoral (Novartis, Switzerland), in a Middle Eastern population, even though both formulations were found to be bioequivalent earlier in a Brazilian population (data on file). It was designed as a randomized, open label, two-way crossover study in which 30 fasting, healthy male volunteers received a single 100 mg cyclosporine dose with 240 ml of water on two treatment days separated by a 1 week washout period. After dosing, serial blood samples were collected for a period of 24 h. Plasma was analyzed for cyclosporine A by a sensitive, reproducible and accurate HPLC method with MS detection capable of detecting cyclosporine A in the range of 5-400 ng/ml with a limit of quantitation of 5 ng/ml. Various pharmacokinetic parameters including AUC(0-t), AUC(0- proportional, variant ), C(max), T(max), T(1/2), and lambda(Z) were determined from plasma concentrations of both formulations. AUC(0-t), AUC(0- proportional, variant ), and C(max) were tested for bioequivalence after log-transformation of data. No significant difference was found based on ANOVA; 90% confidence intervals (82.98-110.57% for AUC(0-t), 81.57-124.71% for AUC(0- proportional, variant ), 80.15-98.91% for C(max)) for these parameters were found to be within the bioequivalence acceptance range of 80-125%. Based on these statistical inferences, it was concluded that Sigmasporin Microoral is bioequivalent to Sandimmun Neoral.