Bioequivalence of rifampicin when administered as a fixed-dose combined formulation of four drugs versus separate formulations

A bioequivalence study of the antitubercular drug rifampicin in a four-drug combination (rifampicin, isoniazid, pyrazinamide and ethambutol) and separ ate formulations of the drugs at the same dose levels was carried out in a group of 22 healthy male volunteers. The investigation was designed as an o pen crossover study. The drugs were administered once in individual formula tions and once in a fixed-dose combination. The WHO-approved protocol was f ollowed according to which six blood samples were collected over a period o f 8 h for each volunteer and each experimental session. Pooled urine sample s were also collected during the study. Rifampicin and desacetyl rifampicin concentrations in both plasma nd urine samples were assessed. Various phar macokinetic parameters such as AUC(0-8h), C-max and T-max were calculated f or both rifampicin and desacetyl rifampicin. The results indicated that com bined (th four-drug combination) and separate formulations are bioequivalen t for rifampicin. (C) 2000 Prous Science, All rights reserved.