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由于利托那韦(ritonavir,蛋白酶抑制剂)和甲红霉素(用于治疗由结核分支杆菌综合征引起的播散性感染)有可能同时合用以治疗感染HIV者和艾滋病患者,故有必要评估这两种药物可能存在的药物相互作用。在很大程度上,甲红霉素和利托那韦不仅都通过细胞色素P450介导的生物转换作用进行代谢,而且又是这些酶的潜在抑制剂。为了评估利托那韦和甲红霉素多剂量给药的药代动力学影响而进行了该项研究。本文采用开放性、随机、三阶段交叉试验。给22位健康志愿者分3个阶段分别单独服用利托那韦(每8h200mg),单独服用甲红霉素(每12h500mg),合用利托那韦和甲红霉素。于第4天收集血样,测定利托那韦、甲红霉素及其代谢产物14-R-羟基甲红霉素。 结果显示,实际上利托那韦完全抑制了14-R-羟基甲红霉素的形成。由于与利托那韦合用,甲红霉素的平均AUC增大了77％,平均终末t_(1/2)从5h延迟到14h,血药峰值上升了31％,血药谷值上升了182％,均有统计学意
Since ritonavir (protease inhibitor) and clarithromycin (used to treat disseminated infections caused by Mycobacterium tuberculosis syndrome) are likely to be used in combination to treat people living with HIV and AIDS, it is necessary Assess the possible drug interactions between the two drugs. To a large extent, both erythromycin and ritonavir are not only metabolized by cytochrome P450-mediated biotransformation, but are also potential inhibitors of these enzymes. The study was conducted to assess the pharmacokinetic effects of multiple doses of ritonavir and clarithromycin. This article uses an open, random, three-phase cross-test. Ritonavir (200 mg every 8h), clarithromycin alone (500mg every 12h), ritonavir and clarithromycin were administered to 22 healthy volunteers in 3 separate phases. Blood samples were collected on day 4 for the determination of ritonavir, clarithromycin, and their metabolites 14-R-hydroxyribacillin. The results showed that in fact ritonavir completely inhibited the formation of 14-R-hydroxy-clarithromycin. Due to its combination with ritonavir, the average AUC of erythromycin increased by 77%. The average terminal t_ (1/2) was delayed from 5h to 14h, the peak blood level increased by 31%, and the plasma trough increased 182%, all statistically significant