Artemisinin and thiabendazole are potent inhibitors of cytochrome P450 1A2 (CYP1A2) activity in humans
Artemisinin and thiabendazole are potent inhibitors of cytochrome P450 1A2 (CYP1A2) activity in humans
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DOI：
10.1007/s00228-005-0037-3
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发表时间：
2005-11-01
影响因子：
2.9
通讯作者：
Masimirembwa, CM
中科院分区：
文献类型：
--
作者：
Bapiro, TE;Sayi, J;Masimirembwa, CM
目的：鉴于青蒿素和噻苯咪唑在体外对同种型具有强效抑制作用，研究青蒿素和噻苯咪唑在人体内引起涉及细胞色素P450（CYP 1A 2）的药代动力学相互作用的可能性。研究方法：10名健康志愿者接受咖啡因（136.5 mg），48 h洗脱期后，志愿者被给予咖啡因片剂（136.5 mg）和噻苯咪唑（500 mg）。再过14天，志愿者们接受了咖啡因和青蒿素（500毫克）。每次给药后，采集血浆直至给药后24 h。采用HPLC-UV和MS检测法测定药物的血药浓度。结果如下：使用4小时后副黄嘌呤与咖啡因的比率作为CYP 1A 2活性的指标，噻苯咪唑和青蒿素分别抑制92%和66%的酶活性。此外，咖啡因的药代动力学在药物存在下发生改变; AUC（0-24）增加1.6倍（P
Objective: To investigate the likelihood of artemisinin and thiabendazole causing pharmacokinetic interactions involving cytochrome P450 (CYP1A2) in humans given their potent inhibitory effects on the isoform in vitro. Methods: Ten healthy volunteers received caffeine (136.5 mg), and after a washout period of 48 h, the volunteers were given a caffeine tablet (136.5 mg) together with thiabendazole (500 mg). After an additional 14 days, the volunteers received caffeine together with artemisinin (500 mg). After each treatment, plasma was obtained up to 24 h post-dose. The plasma concentrations of the drugs were measured by HPLC with UV and MS detection. Results: Using the ratio of paraxanthine to caffeine after 4 h as an indicator of CYP1A2 activity, thiabendazole and artemisinin inhibited 92 and 66%, respectively, of the enzyme activity in vivo. In addition, the pharmacokinetics of caffeine were altered in the presence of the drugs; increases in AUC(0-24) of 1.6-fold (P