Bioequivalence of a novel oral metronidazole formulation

Abstract

The plasma pharmacokinetics of metronidazole (CAS 443-48-1) and its active OH-metabolite (CAS 4812-40-2) were investigated in 16 healthy volunteers after the oral administration of single oral doses of 500 mg metronidazole by means of a novel (test, T) and reference formulation (reference, R). The trial was conducted according to a randomised, controlled, open, within-subject cross-over design with two periods one week apart for wash-out. A single oral dose of 500 mg metronidazole by means of the test formulation T (Vagimid Dragees) resulted in a geometric mean C(max) of 10649 ng/ mL (CV: 0.21) for metronidazole after a median t(max) of 70 min (range: 40 to 120); the geometric mean of the AUC(0-t(z)) and AUC(0-infinity) were 107406 (CV: 0.25) and 109056 ng x h/mL (CV: 0.26); the arithmetic mean of the half-life (t1/2) and the mean residence time (MRT) were 7.28 h (CV: 0.12) and 11.62 h (CV: 0.10). For the OH-metabolite, the geometric mean C(max) was 1941 ng/mL (CV: 0.22) after a median t(max) of 480 min (range: 360 to 600) with a geometric mean AUC(0-tz) and AUC(0-infinity) of 48653 (CV: 0.21) and 52417 ng x h/mL (CV: 0.22), respectively; the arithmetic mean t1/2 and MRT were 10.60 h (CV: 0.21) and 21.14 h (CV: 0.13), respectively. The test formulation was bioequivalent with the reference formulation for both metronidazole (90% CI of the treatment ratio of 1.02 to 1.15 and 1.02 to 1.12 for C(max) and AUC) and its metabolite (90% CI of 0.92 to 1.05 and 0.98 to 1.06, respectively). The treatments were very well tolerated and there were no limiting safety-relevant findings.