PHARMACOKINETIC VARIABILITY OF ZIDOVUDINE IN HIV-INFECTED INDIVIDUALS - SUBGROUP ANALYSIS AND DRUG-INTERACTIONS
PHARMACOKINETIC VARIABILITY OF ZIDOVUDINE IN HIV-INFECTED INDIVIDUALS - SUBGROUP ANALYSIS AND DRUG-INTERACTIONS
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DOI：
10.1097/00002030-199412000-00007
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发表时间：
1994-12-01
期刊：
影响因子：
3.8
通讯作者：
BEIJNEN, JH
中科院分区：
文献类型：
--
作者：
BURGER, DM;MEENHORST, PL;BEIJNEN, JH
目的：研究HIV感染患者中Zidovudine（ZDV）药代动力学的个体间和内部变异性的决定因素。设计：一家525张病床医院的前瞻性研究，并具有特殊的HIV感染患者治疗和研究的特殊资金。从68个感染HIV的个体中收集了连续血样，总共提供95个药代动力学曲线。用高性能液相色谱和放射免疫测定法测量ZDV。通过非室内分析计算药代动力学参数。通过多变量分析对患者特征进行了对ZDV药代动力学的影响。分析：体重较低的患者，女性以及患有更晚期HIV疾病的患者的ZDV清除率明显降低。美沙酮与ZDV的共同给药会导致较高的血浆ZDV浓度，而利福平和Ganciclovir则增加了明显的ZDV清除率。年龄，ZDV使用的持续时间，CD4+细胞计数，肌酐清除率，血清肝酶水平升高以及其他11种共同管理药物的使用与明显的ZDV清除无关。已经评估了ZDV与14种不同药物或组的药物 - 药物相互作用的观察毒品。这些数据表明，一旦建立了药代动力学 - 药物动力学关系，患者个性化的抗逆转录病毒疗法可能是合适的。
Objective: To investigate determinants of inter- and intraindividual variability of zidovudine (ZDV) pharmacokinetics in HIV-infected patients.Design: A prospective study in a general 525-bed hospital with special funding for treatment and research of HIV-infected patients.Methods: Serial blood samples were collected from 68 HIV-infected individuals providing a total of 95 pharmacokinetic curves. ZDV was measured with high-performance liquid chromatography and radioimmunoassay. Pharmacokinetic parameters were calculated by non-compartmental analysis. Patient characteristics were investigated by multivariate analysis for an influence on ZDV pharmacokinetics.Results: Apparent ZDV clearance was significantly lower in patients with a lower body weight, in women, and in patients with a more advanced stage of HIV disease. Co-administration of methadone with ZDV resulted in higher plasma concentrations of ZDV, while rifampin and ganciclovir increased apparent ZDV clearance. Age, the duration of ZDV use, CD4+ cell count, creatinine clearance, elevated serum liver enzyme levels, and the use of 11 other co-administered medications were not independently related to apparent ZDV clearance.Conclusions: The pharmacokinetic profile of ZDV in several subpopulations has been evaluated, as well as the observation of possible drug-drug interactions between ZDV and 14 different drugs or groups of drugs. These data suggest that patient-individualized antiretroviral therapy may be appropriate once pharmacokinetic-pharmacodynamic relationships have been established.