Lunn D J, Aarons L
Department of Epidemiology and Public Health, Imperial College School of Medicine at St. Mary's, London, United Kingdom.
J Pharmacokinet Biopharm. 1998 Feb;26(1):47-74. doi: 10.1023/a:1023224824228.
Saquinavir is an HIV proteinase inhibitor marketed as a treatment for HIV infection. The drug has potent (Ki approximately 0.1 nM) antiviral activity and acts by inhibiting the processing of gag and gag-pol polyproteins, thus blocking the maturation of replicated viral particles. By assuming standard two-compartment disposition kinetics in combination with a variety of absorption processes we have identified two structural models that perform well with respect to describing the pharmacokinetic behavior of saquinavir when administered to healthy human volunteers from various Phase I studies. These structural models have been implemented for population analysis of these Phase I data via the Bayesian Markov chain Monte Carlo approach. We conclude that saquinavir exhibits complex and highly variable behavior, but can be modeled adequately using a two-compartment zero-order absorption model. There is also an indication that saquinavir kinetics may be time-dependent.
沙奎那韦是一种作为治疗HIV感染的药物上市的HIV蛋白酶抑制剂。该药物具有强效（Ki约为0.1 nM）的抗病毒活性，其作用机制是抑制gag和gag-pol多聚蛋白的加工，从而阻断复制的病毒颗粒的成熟。通过假设标准的二室处置动力学并结合多种吸收过程，我们确定了两种结构模型，在描述来自各种I期研究的健康人类志愿者服用沙奎那韦后的药代动力学行为方面表现良好。这些结构模型已通过贝叶斯马尔可夫链蒙特卡罗方法用于这些I期数据的群体分析。我们得出结论，沙奎那韦表现出复杂且高度可变的行为，但可以使用二室零级吸收模型进行充分建模。还有迹象表明沙奎那韦的动力学可能是时间依赖性的。
