Vanhove G F, Kastrissios H, Gries J M, Verotta D, Park K, Collier A C, Squires K, Sheiner L B, Blaschke T F
Division of Clinical Pharmacology, Stanford University, California, USA.
Antimicrob Agents Chemother. 1997 Nov;41(11):2428-32. doi: 10.1128/AAC.41.11.2428.
We investigated the pharmacokinetics of zidovudine, zalcitabine, and saquinavir in AIDS Clinical Trial Group protocol 229. Patients received either saquinavir, zalcitabine, or a combination of both, together with zidovudine three times a day. Approximately 100 patients were enrolled in each treatment arm, and intensive pharmacokinetic studies were performed on about 25 patients per arm at weeks 1 and 12. We estimated the pharmacokinetic parameters of all three drugs by using parametric and nonparametric methods. The mean values of the pharmacokinetic parameters of zidovudine (clearance [CL]/bioavailability [F], 168 liters/h; volume of distribution [V]/F, 185 liters; half-life, 0.76 h) and zalcitabine (CL/F, 25 liters/h; V/F, 92.2 liters; half-life, 2.7 h) were similar to those reported previously. For saquinavir, the mean pharmacokinetic parameter estimates using parametric methods were as follows: maximum concentration of drug in serum [Cmax], 70.8 ng/ml; time to Cmax, 3.11 h; area under the curve, 809 ng x h/ml; CL/F, 989 liters/h; V/F, 1,503 liters; half-life, 1.38 h. For all three drugs, clearance decreased with age. Weight did not influence the clearance of zidovudine, but the clearance of zalcitabine and saquinavir increased with weight. There were no differences in pharmacokinetic parameters between study weeks and arms, suggesting that there is no change in kinetics with chronic administration and that there are no significant pharmacokinetic interactions among these three drugs.
我们在艾滋病临床试验组方案229中研究了齐多夫定、扎西他滨和沙奎那韦的药代动力学。患者接受沙奎那韦、扎西他滨或两者的组合，同时每日3次服用齐多夫定。每个治疗组约有100名患者入组，在第1周和第12周时对每组约25名患者进行了深入的药代动力学研究。我们使用参数法和非参数法估计了所有三种药物的药代动力学参数。齐多夫定（清除率[CL]/生物利用度[F]，168升/小时；分布容积[V]/F，185升；半衰期，0.76小时）和扎西他滨（CL/F，25升/小时；V/F，92.2升；半衰期，2.7小时）的药代动力学参数平均值与先前报道的相似。对于沙奎那韦，使用参数法估计的平均药代动力学参数如下：血清中药物的最大浓度[Cmax]，70.8纳克/毫升；达Cmax的时间，3.11小时；曲线下面积，809纳克·小时/毫升；CL/F，989升/小时；V/F，1503升；半衰期，1.38小时。对于所有三种药物，清除率均随年龄增长而降低。体重不影响齐多夫定的清除率，但扎西他滨和沙奎那韦的清除率随体重增加而升高。研究周数和治疗组之间的药代动力学参数没有差异，这表明长期给药时动力学没有变化，且这三种药物之间没有显著的药代动力学相互作用。
