Pharmacokinetics of orally administered zidovudine among patients with hemophilia and asymptomatic human immunodeficiency virus (HIV) infection.
Pharmacokinetics of orally administered zidovudine among patients with hemophilia and asymptomatic human immunodeficiency virus (HIV) infection.
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血友病和无症状人类免疫缺陷病毒（HIV）感染患者口服齐多夫定的药代动力学。
DOI：
10.1016/0166-3542(89)90008-9
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发表时间：
1989
影响因子：
7.6
通讯作者：
Reichman,RC
中科院分区：
文献类型：
--
作者：
Morse,GD;Olson,J;Portmore,A;Taylor,C;Plank,C;Reichman,RC
齐多夫定（以前称为叠氮胸苷，AZT）用于治疗某些感染人类免疫缺陷病毒（HIV）的患者。然而，齐多夫定（ZDV）在血友病患者中的临床使用可能会因该患者人群中慢性肝炎的高发病率而复杂化。为了检查ZDV的药代动力学，8名无症状HIV感染的血友病患者接受了单次口服剂量（300 mg）。采用HPLC法测定血清中ZDV及其葡糖苷酸代谢产物（GZDV）。ZDV吸收迅速，在0.5 h时血药浓度达峰（2052 ± 970 ng/ml）。1 h时GZDV血清峰浓度为4751 ± 2269 ng/ml。ZDV和GZDV在4小时内均以双指数方式下降。4 h后，3例患者的ZDV血清浓度继续呈对数线性下降，而5例患者显示三指数曲线，其平均终末消除半衰期为4.8 ± 2.8 h。未观察到ZDV或GZDV动力学与肝酶升高程度之间的关系。尽管ZDV的治疗窗口尚未描述，但标准剂量引起的广泛血清浓度表明ZDV水平的临床监测在某些患者中可能有价值。此外，本研究中ZDV的消除半衰期延长可能为某些患者的给药频率降低提供了依据。
Zidovudine (formerly azidothymidine, AZT) is used to treat certain patients infected with the human immunodeficiency virus (HIV). However, the clinical use of zidovudine (ZDV) in hemophilia patients may be complicated by the high incidence of chronic hepatitis in this patient population. To examine the pharmacokinetics of ZDV eight asymptomatic HIV-infected hemophilia patients received a single oral dose (300 mg). ZDV and its glucuronide metabolite (GZDV) were measured in serum by HPLC. ZDV was rapidly absorbed with a wide range of peak serum concentrations (2052 ± 970 ng/ml) at 0.5 h. Peak GZDV serum concentrations were 4751 ± 2269 ng/ml at 1 h. Both ZDV and GZDV declined in a biexponential manner over 4 h. After 4 h, the ZDV serum concentration decay in three patients continued a log-linear decline, while five patients demonstrated a tri-exponential curve which had a mean terminal elimination half-life of 4.8 ± 2.8 h. No relationship between ZDV or GZDV kinetics and the degree of hepatic enzyme elevation was observed. Although a therapeutic window for ZDV has yet to be described, the wide range of serum concentrations that result from a standard dose suggests that clinical monitoring of ZDV levels may be of value in certain patients. In addition, the prolonged elimination half-life of ZDV in the present study may provide a rationale for less frequent dosing in certain patients.