Sugimoto K, Sakamoto K, Fujimura A
Department of Clinical Pharmacology, Jichi Medical School, Tochigi, Japan.
Life Sci. 1997;60(3):173-9. doi: 10.1016/s0024-3205(96)00613-3.
To assess the pharmacokinetic interaction of cyclosporin A with probucol, we administered cyclosporin A (10 mg/kg body weight) to rats orally or intravenously with or without pretreatment of probucol (10 mg/animal, daily for 8 days). The whole blood cyclosporin A concentration-time curves after oral administration showed a 34% reduction in peak concentration and a 30% decrease in area under the blood concentration-time curve (AUC) by administration of probucol. No apparent change in elimination half-life or volume of the central compartment was observed with the treatment of probucol. After intravenous administration of cyclosporin A, the blood levels could be described by a two-compartment open model. No differences were observed in the AUC, elimination half-life or total clearance of cyclosporin A by the pretreatment of probucol. Calculated bioavailability following oral administration of cyclosporin A decreased by 33% with the treatment of probucol. These results suggest that probucol may not profoundly influence the disposition of cyclosporin A. Coadministration of probucol could decrease the fraction of absorbed cyclosporin A after oral administration.
为评估环孢素A与普罗布考之间的药代动力学相互作用，我们给大鼠口服或静脉注射环孢素A（10毫克/千克体重），同时大鼠接受或不接受普罗布考预处理（10毫克/只动物，每日给药，共8天）。口服给药后，全血中环孢素A的浓度-时间曲线显示，给予普罗布考后，峰浓度降低了34%，血药浓度-时间曲线下面积（AUC）降低了30%。普罗布考治疗后，消除半衰期或中央室容积未见明显变化。静脉注射环孢素A后，血药浓度可用二室开放模型描述。普罗布考预处理后，环孢素A的AUC、消除半衰期或总清除率均未观察到差异。口服环孢素A后计算得到的生物利用度在普罗布考治疗后降低了33%。这些结果表明，普罗布考可能不会对环孢素A的处置产生深远影响。普罗布考与环孢素A合用时，可降低口服给药后环孢素A的吸收分数。
