Bioequivalence of fixed-dose combination Myrin®-P Forte and reference drugs in loose combination

BACKGROUND: Myrin®-P Forte is a fixed-dose combination (FDC) tablet containing rifampicin (RMP, 150 mg), isoniazid (INH, 75 mg), ethambutol (EMB) hydrochloride (275 mg) and pyrazinamide (PZA, 400 mg) developed for the treatment of tuberculosis (TB).SETTING: This study was conducted at a single centre-the Pfizer Clinical Research Unit in Singapore.OBJECTIVE: To demonstrate the bioequivalence of each drug component of the Myrin-P Forte FDC and the individual product in loose combination.DESIGN: In a randomized, open-label, single-dose, two-way, crossover study, subjects received single doses of Myrin-P Forte or four individual products under fasting conditions in a crossover fashion with at least 7 days washout between doses. The primary measures for comparison were peak plasma concentration (Cmax) and the area under plasma concentration-time curve (AUC).RESULTS: Of 36 subjects enrolled, 35 completed the study. The adjusted geometric mean ratios and 90% confidence intervals for Cmax and AUC values were completely contained within bioequivalence limits (80%, 125%) for all four drugs in both formulations. Both treatments were generally well tolerated in the study.CONCLUSION: The Myrin-P Forte FDC tablet formulation is bioequivalent to the four single-drug references for RMP, INH, EMB hydrochloride and PZA at equivalent doses.