Gallicano K, Sahai J, Ormsby E, Cameron D W, Pakuts A, McGilveray I
Bureau of Drug Research, Health & Welfare Canada, Ottawa.
Br J Clin Pharmacol. 1993 Aug;36(2):128-31. doi: 10.1111/j.1365-2125.1993.tb04208.x.
The pharmacokinetics of zidovudine in 10 symptomatic HIV-infected men were assessed after administration of the initial 200 mg oral dose at the start of therapy (day 1) and on one occasion during non steady-state conditions of chronic-dose therapy (200 mg every 4 h while awake on day 21-66; 5 doses per day). The following mean (+/- s.d.) pharmacokinetic parameters were determined on day 1 and during chronic therapy, respectively: Cmax (4.09 +/- 2.54 vs 3.82 +/- 1.03 mumol l-1), oral clearance (40.7 +/- 12.9 vs 41.1 +/- 8.4 ml min-1 kg-1) and terminal half-life (68.4 +/- 29.4 vs 65.1 +/- 13.1 min). Mean pharmacokinetic parameters on day 1 were < 10% different (P > 0.34) from those determined during chronic therapy. Differences in means of 21% for clearance and 36% for Cmax could be detected with a power of 80% at the 5% significance level. Intra-subject coefficients of variation were 17% for clearance and 32% for Cmax, respectively. This study suggests that within a group of patients whose stage of HIV infection and general health are relatively stable, first-dose pharmacokinetic parameters provide a good estimate of multiple-dose pharmacokinetic parameters.
在治疗开始时（第1天）给予10名有症状的HIV感染男性初始200mg口服剂量，并在慢性剂量治疗的非稳态条件下（第21 - 66天清醒时每4小时200mg；每天5次剂量）的某一时刻评估齐多夫定的药代动力学。分别在第1天和慢性治疗期间测定了以下平均（±标准差）药代动力学参数：Cmax（4.09±2.54对3.82±1.03μmol l-1）、口服清除率（40.7±12.9对41.1±8.4ml min-1 kg-1）和末端半衰期（68.4±29.4对65.1±13.1分钟）。第1天的平均药代动力学参数与慢性治疗期间测定的参数相差<10%（P>0.34）。在5%显著性水平下，80%的检验效能可检测到清除率均值相差21%，Cmax均值相差36%。受试者内清除率变异系数和Cmax变异系数分别为17%和32%。本研究表明，在一组HIV感染阶段和总体健康状况相对稳定的患者中，首剂药代动力学参数可很好地估计多剂药代动力学参数。
