Abstract
Metronidazole is a BCS (Biopharmaceutics Classification System) class 1 drug, traditionally
considered the choice drug in the infections treatment caused by protozoa and anaerobic
microorganisms. This study aimed to evaluate bioequivalence between 2 different marketed
250 mg metronidazole immediate release tablets. A randomized, open-label, 2×2 crossover
study was performed in healthy Brazilian volunteers under fasting conditions with
a 7-day washout period. The formulations were administered as single oral dose and
blood was sampled over 48 h. Metronidazole plasma concentrations were determined by
a liquid chromatography mass spectrometry (LC-MS/MS) method. The plasma concentration
vs. time profile was generated for each volunteer and the pharmacokinetic parameters
Cmax, Tmax, AUC0–t, AUC0–∞, ke, and t1/2 were calculated using a noncompartmental model. Bioequivalence between pharmaceutical
formulations was determined by calculating 90% CIs (Confidence Intervall) for the
ratios of Cmax, AUC0–t, and AUC0–∞ values for test and reference using log-transformed data. 22 healthy volunteers (11
men, 11 women; mean (SD) age, 28 (6.5) years [range, 21–45 years]; mean (SD) weight,
66 (9.3) kg [range, 51–81 kg]; mean (SD) height, 169 (6.5) cm [range, 156–186 cm])
were enrolled in and completed the study. The 90% CIs for Cmax (0.92–1.06), AUC0–t (0.97–1.02), and AUC0–∞ (0.97–1.03) values for the test and reference products fitted in the interval of
0.80–1.25 proposed by most regulatory agencies, including the Brazilian agency ANVISA.
No clinically significant adverse effects were reported. After pharmacokinetics analysis,
it concluded that test 250 mg metronidazole formulation is bioequivalent to the reference
product according to the Brazilian agency requirements.
Key words
metronidazole - human plasma - bioequivalence - biowaiver - HPLC-MS/MS
