甘氨双唑钠在大鼠和小鼠体内药代动力学

PHARMACOKINETICS OF SODIUM BIMETRONDAZOLE GLYCINATE IN MICE AND RATS

目的 观察甘氨双唑钠 (CMNa)在动物体内的药代动力学。方法 采用HPLC方法测定生物样品中CMNa及其代谢物甲硝唑的含量。结果 小鼠体外转化试验表明血中 90minCMNa的转化率为 91 8% ,甲硝唑的生成率为 6 7 3 %。小鼠ivCMNa 5 7 3,171 9和 5 15 7mg·kg-1后CMNa的T1/2 β约为 1 0min ,甲硝唑的T1/2 β约为 6 0min。大鼠ivCMNa 171 9mg·kg-1后 2min及 5minCMNa及甲硝唑在组织含量较高 ;药后从尿中排泄的CMNa和甲硝唑分别占给药总量的 8 4%和 16 7% ,从胆汁排泄分别占 11 5 %和 5 1% ,从粪排泄占 0 14%和0 0 3%。CMNa平均血浆蛋白结合率为 14 2 %。结论 CMNa在体内迅速代谢为甲硝唑 ,原型药及代谢物的Cmax和AUC均与剂量正相关 ,二者主要经尿和胆汁排泄。

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 iv doses of 57 3, 171 9 and 515 7 mg·kg -1 CMNa in mice, the T 1/2 β of the parent drug was 0 5, 0 8 and 1 0 min, the T 1/2 β of metronidazole was 63 2, 68 2 and 64 3 min. After a single iv 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 C max and AUC of the parent drug and metronidazole increased proportionally with increasing doses. CMNa and metronidazole were predominantly excreted with the urine and bile.