Bioequivalence of compound rifampicin dual-release capsules

Objective To evaluate bioequivalence of the combination component rifampicin,isoniazid,pyrazinamide,ethambutol of the anti-tuberculosis fixed-dose combination of compound rifampicin dual-release capsules(test formulation) and commercially available preparation(reference preparation).Methods Twenty Chinese healthy male volunteers were randomly divided into two groups,with 10 volunteers in each groups.The observation group was given 12 compound rifampicin dual-release capsules and control group was given reference preparation.One week after their own cross,another kind of preparation was administrated.The concentrations of rifampicin,isoniazid and pyrazinamide in plasma were determined by high performance liquid chromatography,the urine concentration of ethambutol was determined by UV-visible spectrophotometry and the pharmacokinetic parameters were calculated by 3P97 software.Results There were significant differences in tmax,AUC0-t,AUC0-∞(P0.05) and there was no significant difference in Cmax(P0.05) in rifampicin between two groups.There were no significant differences in tmax,Cmax,AUC0-t and AUC0-∞ in isoniazid and pyrazinamide between two groups(P0.05).The cumulative urinary excretion of ethambutol was(70.99±21.00)% and(65.03±18.00)% in test formulation and reference preparation(P0.05),respectively.The relative bioavailability of rifampicin,isoniazid,pyrazinamide and ethambutol was(126.8±18.2)%,(109.9±14.2)%,(116.8±17.5)%,and(109.2±46.0)% in test formulation compared with that in reference preparation,respectively.Conclusion Rifampicin does not show bioequivalence between the two formulations,meanwhile isoniazid,pyrazinamide and ethambutol in the two formulations are bioequivalent.