Multiple-dose pharmacokinetics of oral zidovudine in hemophilia patients with human immunodeficiency virus infection.
Multiple-dose pharmacokinetics of oral zidovudine in hemophilia patients with human immunodeficiency virus infection.
复制标题
人类免疫缺陷病毒感染的血友病患者口服齐多夫定的多剂量药代动力学。
DOI：
10.1128/aac.34.3.394
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发表时间：
1990
影响因子：
4.9
通讯作者：
Reichman,RC
中科院分区：
文献类型：
--
作者：
Morse,GD;Portmore,A;Olson,J;Taylor,C;Plank,C;Reichman,RC
对8例感染人类免疫缺陷病毒的无症状血友病患者慢性口服给药（清醒时每4小时300 mg） 12周，检查齐多夫定（ZDV）的配置情况。在开始给药时、6周和12周后进行药代动力学研究。基线肝功能检查显示胆红素、白蛋白和凝血酶原时间正常，而肝酶水平为正常水平的一至三倍。最初，血浆中ZDV浓度的平均峰值为2,052 ng/ml，范围为1,033至3,907 ng/ml，而在慢性给药期间，第6周和第12周的峰值分别为1,619 +/- 1,062 ng/ml和1,711 +/- 786 ng/ml。第1周、第6周和第12周，4 h时ZDV浓度分别降至77 +/- 53 ng/ml、110 +/- 43 ng/ml和101 +/- 49 ng/ml。最初，3名患者的血浆浓度与时间衰减呈线性关系，平均半衰期（t1/2）为1.3 +/- 0.5小时，而5名患者在4小时后血浆中可检测到浓度，终末期t1/2明显延迟，为4.8 +/- 2.8小时。在第6周，所有患者都注意到延长的消除模式（t1/2终末期= 4.1 +/- 2.0小时）。肝酶水平与t1/2无相关性。这些发现表明，在多次给药期间，ZDV可能表现出延长的消除期。进一步的研究利用更敏感的分析可能有助于进一步确定ZDV消除的后期阶段。
The disposition of zidovudine (ZDV) was examined during chronic oral dosing (300 mg every 4 h while awake) for 12 weeks in eight asymptomatic patients with hemophilia who were infected with the human immunodeficiency virus. Pharmacokinetic studies were conducted at the initiation of drug administration and after 6 and 12 weeks. Baseline liver function tests indicated normal values for bilirubin, albumin, and prothrombin time, while hepatic enzyme levels ranged from one to three times the normal levels. Initially, the mean peak ZDV concentration in plasma was 2,052 ng/ml with a range of 1,033 to 3,907 ng/ml, while during chronic dosing the peaks were 1,619 +/- 1,062 ng/ml and 1,711 +/- 786 ng/ml at weeks 6 and 12, respectively. ZDV concentrations at 4 h declined to 77 +/- 53 ng/ml, 110 +/- 43 ng/ml, and 101 +/- 49 ng/ml at weeks 1, 6, and 12, respectively. Initially, the plasma concentration-versus-time decay in three patients was linear, with a mean half-life (t1/2) of 1.3 +/- 0.5 h, while five patients had detectable concentrations in plasma after 4 h with an apparent delayed terminal-phase t1/2 of 4.8 +/- 2.8 h. At week 6 the prolonged elimination pattern was noted in all patients (terminal t1/2 = 4.1 +/- 2.0 h). No correlation between hepatic enzyme levels and t1/2 was noted. These findings suggest that ZDV may display a prolonged elimination phase during multiple dosing. Further studies utilizing a more sensitive assay may help to further define this later phase of ZDV elimination.