Key result
Test metronidazole product demonstrates bioequivalence to the commercial reference product.
Why the study?
A sensitive, accurate, rapid, and reproducible HPLC method for determining metronidazole levels in human plasma was needed for bioequivalence studies.
Is the test metronidazole product bioequivalent to the commercial reference product in healthy volunteers?
RCT (n=24)
Randomized
No
Is the test metronidazole product bioequivalent to the commercial reference product in healthy volunteers?
Effect estimate: Test/reference ratio 90% CI 0.973-1.051 (95% CI 0.973-1.051)
Absolute Event Rate: 124.6% vs 122.3%
p-value: p=NS
A new HPLC method was successfully developed and applied to demonstrate bioequivalence between a test and reference metronidazole product.
Supports substitution of the test metronidazole product; confirms bioequivalence and validates the new HPLC method for future pharmacokinetic studies.
Purpose: To develop new sensitive, accurate, rapid and reproducible high performance liquid chromatography (HPLC) method to determine metronidazole levels in human plasma and to apply the method in a bioequivalence study.Methods: Metronidazole was extracted from human plasma through one step of protein precipitation by methanol using carbamazepine as internal standard (IS). After centrifugation of the plasma sample, the supernatant layer was separated and injected into HPLC system using Eclipse XDB-phenyl column. The mobile phase consisted of phosphate buffer (pH 4.5): acetonitrile (95:5, v/v). The UV detector was set at 320 nm. The bioavailability of the test metronidazole product (Brand A) was compared to a commercial metronidazole brand as reference product in 24 healthy volunteers who received a single dose equivalent to 500 mg of the test and reference products in a randomized balanced two-way cross-overdesign separated by two-week wash-out period.Results: Mean standard calibration curves of metronidazole over the concentration range of 0.05 . 30 ƒÊg/ml were linear. No significant differences were found based on analysis of variance of the pharmacokinetics parameters required for the assessment of bioequivalence of test and reference formulations. The mean value and 90 %CI of test/reference ratios for the derived parameters were: Cmax, 9.64 vs. 8.38 (0.93 . 1.10), AUC0-24, 124.6 vs.122.3 ƒÊg.h/mL (0.973 . 1.051) and AUC0-‡, 140.9 vs. 128.4 h/mL (1.15 . 1.23).Conclusion: The test metronidazole product was bioequivalent to the reference. The method is suitable for bioequivalence and pharmacokinetic studies in humans with a low limit of quantification of 0.05 ƒÊg/ml.
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TM El-Nahhas (2013) conducted an RCT in Healthy volunteers (n=24). Metronidazole (Brand A) vs. Metronidazole (Flagyl) was evaluated on AUC 0-24 (Test/reference ratio 90% CI 0.973-1.051, 95% CI 0.973-1.051, p=NS). The test metronidazole product was bioequivalent to the reference product, with the 90% confidence interval for the AUC 0-24 test/reference ratio (0.973-1.051) falling within the acceptance range.
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