title: 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.
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, MHAPT "Zaritza Johanna" University Hospital, Sofia, Bulgaria.
authors.forename: Emil
authors.initials: E
authors.lastname: Gatchev
authors.forename: Manfred
authors.initials: M
authors.lastname: Bräter
authors.forename: Christian
authors.initials: C
authors.lastname: de Mey
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000994:Antitrichomonal Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D001711:Biotransformation; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D005260:Female; D006207:Half-Life; D006801:Humans; D006900:Hydroxylation; D008297:Male; D008795:Metronidazole / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D008875:Middle Aged; D013056:Spectrophotometry, Ultraviolet; D013810:Therapeutic Equivalency
chemical_list: D000994:Antitrichomonal Agents; D008795:Metronidazole