Gitterman S R, Drusano G L, Egorin M J, Standiford H C
Department of Medicine, University of Maryland Cancer Center, Baltimore.
Clin Pharmacol Ther. 1990 Aug;48(2):161-7. doi: 10.1038/clpt.1990.131.
The epidemic of human immunodeficiency virus infection has forced an unprecedented acceleration of drug development. The lack of effective therapy at present against many of the infectious complications of acquired immunodeficiency syndrome (AIDS) has forced the rapid clinical introduction of new agents. Population pharmacokinetic models are particularly attractive as a means of assessing drug disposition in cohorts different from those studied during necessarily abbreviated phase I trials. We have used the population pharmacokinetics model as implemented by the computer program NONMEM to study the distribution of zidovudine in a large number of patients who have AIDS-related complex and who are therefore at an earlier stage of immunosuppression than subjects in other studies. We confirm a clearance of drug identical to that seen by traditional methods but a larger volume of distribution than estimated previously in patients with AIDS. Possible reasons for this discrepancy and the use of this method in the development of antiretroviral therapy are discussed.
人类免疫缺陷病毒感染的流行迫使药物研发以前所未有的速度加速推进。目前针对许多获得性免疫缺陷综合征（艾滋病）感染并发症缺乏有效治疗方法，这促使新药物迅速进入临床应用。群体药代动力学模型作为一种评估药物处置情况的手段，在不同于那些在必然缩短的I期试验中所研究人群的队列中具有特别的吸引力。我们使用由计算机程序NONMEM实现的群体药代动力学模型，来研究齐多夫定在大量患有艾滋病相关综合征患者中的分布情况，这些患者因此处于免疫抑制的早期阶段，比其他研究中的受试者更早。我们证实该药物的清除率与传统方法所见相同，但分布容积比先前估计的艾滋病患者更大。讨论了这种差异的可能原因以及该方法在抗逆转录病毒疗法研发中的应用。
