C X Liu1, G L Wei, S H Xiao. 1. Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China.
Abstract
AIM: To study the pharmacokinetic properties of sodium bimetrondazole glycinate (CMNa) in animals. METHODS: The concentrations of CMNa and its metabolite metronidazole in biological samples were determined by an HPLC method with UV detection. RESULTS: The transformation studies in vitro indicated that the CMNa transformation rate and metronidazole generation rate in whole blood at 90 min were 91.8% and 67.3%, respectively. After single i.v. doses of 57.3, 171.9 and 515.7 mg.kg-1 CMNa in mice, the T1/2 beta of the parent drug was 0.5, 0.8 and 1.0 min, the T1/2 beta of metronidazole was 63.2, 68.2 and 64.3 min. After a single i.v. dose of 171.9 mg.kg-1 CMNa in rats, the levels of CMNa and metronidazole in various tissues were higher at 2 and 5 min. The urinary excretion of the parent drug and metronidazole were 8.4% and 16.7% of the dose, the biliary excretion were 11.5% and 5.1% and the fecal excretion were 0.14% and 0.03%, respectively. The average plasma protein binding ratio (PPBR) of CMNa was 14.2%. CONCLUSION: CMNa was rapidly metabolized into metronidazole in vivo. The levels of Cmax and AUC of the parent drug and metronidazole increased proportionally with increasing doses. CMNa and metronidazole were predominantly excreted with the urine and bile.
AIM: To study the pharmacokinetic properties of sodium bimetrondazole glycinate (CMNa) in animals. METHODS: The concentrations of CMNa and its metabolite metronidazole in biological samples were determined by an HPLC method with UV detection. RESULTS: The transformation studies in vitro indicated that the CMNa transformation rate and metronidazole generation rate in whole blood at 90 min were 91.8% and 67.3%, respectively. After single i.v. doses of 57.3, 171.9 and 515.7 mg.kg-1 CMNa in mice, the T1/2 beta of the parent drug was 0.5, 0.8 and 1.0 min, the T1/2 beta ofmetronidazole was 63.2, 68.2 and 64.3 min. After a single i.v. dose of 171.9 mg.kg-1 CMNa in rats, the levels of CMNa and metronidazole in various tissues were higher at 2 and 5 min. The urinary excretion of the parent drug and metronidazole were 8.4% and 16.7% of the dose, the biliary excretion were 11.5% and 5.1% and the fecal excretion were 0.14% and 0.03%, respectively. The average plasma protein binding ratio (PPBR) of CMNa was 14.2%. CONCLUSION:CMNa was rapidly metabolized into metronidazole in vivo. The levels of Cmax and AUC of the parent drug and metronidazole increased proportionally with increasing doses. CMNa and metronidazole were predominantly excreted with the urine and bile.