Diekmann H W, Schneidereit M, Overbosch D
Instititut für Experimentelle Arzneimittelforschung, E. Merck, Darmstadt, W. Germany.
Acta Leiden. 1989;57(2):217-28.
In order to find ways to increase the usually very low bioavailability of praziquantel, the effect of cytochrome P-450 inhibitors on the metabolism of praziquantel was investigated in rats. Cimetidine, ketoconazole, and miconazole yielded a 90% inhibition of the metabolism of praziquantel in liver microsome preparations from phenobarbital-pretreated rats at concentrations of 2.0, 0.03, and 0.01 mM, respectively. In rats in vivo ketoconazole and miconazole increased the bioavailability of praziquantel by a factor of 2 and 4, respectively in doses of 25 mg/kg. In phenytoin-pretreated rats ketoconazole increased the bioavailability of praziquantel by a factor of 1.4, whereas miconazole yielded a 5-fold increase of the bioavailability. Cimetidine was an effective inhibitor at a dose of 200 mg/kg. These results suggest that the inhibitors tested may suppress the metabolism of praziquantel in humans and consequently increase the bioavailability and blood levels at doses common in human therapy.
为了找到提高吡喹酮通常很低的生物利用度的方法，研究了细胞色素P - 450抑制剂对吡喹酮在大鼠体内代谢的影响。西咪替丁、酮康唑和咪康唑在浓度分别为2.0、0.03和0.01 mM时，对苯巴比妥预处理大鼠的肝微粒体制剂中吡喹酮的代谢产生了90%的抑制作用。在体内，酮康唑和咪康唑在25 mg/kg的剂量下分别使吡喹酮的生物利用度提高了2倍和4倍。在苯妥英预处理的大鼠中，酮康唑使吡喹酮的生物利用度提高了1.4倍，而咪康唑使生物利用度提高了5倍。西咪替丁在200 mg/kg的剂量下是一种有效的抑制剂。这些结果表明，所测试的抑制剂可能会抑制吡喹酮在人体内的代谢，从而在人类治疗常用剂量下提高生物利用度和血药浓度。
