Muret Patrice, Solas Caroline
Laboratoire de Pharmacologie Clinique et Toxicologie, CHU Minjoz, Besançon, France.
Therapie. 2011 May-Jun;66(3):207-12. doi: 10.2515/therapie/2011029. Epub 2011 Aug 9.
The human immunodeficiency virus (HIV) protease inhibitor saquinavir displays a large inter-individual variability in its pharmacokinetic parameters, related to a low absorption rate and an important hepatic metabolism. Based on literature, is the saquinavir therapeutic drug monitoring relevant? In naïve HIV-infected patients, the probability of achieving an undetectable HIV viral load at W48 was significantly associated with a saquinavir plasma trough concentration >100 ng/mL. Two studies in HIV-infected pre-treated patients reported that the genotypic inhibitory quotient was a predictive factor of virologic response with a threshold value around 40 ng/mL/mutation. Concerning the exposure-toxicity relationship, the risk of occurrence of grade 3-4 abdominal pains was more frequently associated with high concentrations of saquinavir, but without threshold value determination. Several studies, one of which was randomized, have reported the interest of saquinavir therapeutic drug monitoring to optimize the virologic response. Therefore, the level of evidence of the interest of saquinavir therapeutic drug monitoring is "recommended".
人类免疫缺陷病毒（HIV）蛋白酶抑制剂沙奎那韦的药代动力学参数存在较大个体差异，这与低吸收率和重要的肝脏代谢有关。根据文献，沙奎那韦的治疗药物监测是否相关？在初治HIV感染患者中，第48周时实现HIV病毒载量不可检测的概率与沙奎那韦血浆谷浓度>100 ng/mL显著相关。两项针对经治HIV感染患者的研究报告称，基因型抑制商是病毒学反应的预测因素，阈值约为40 ng/mL/突变。关于暴露-毒性关系，3-4级腹痛的发生风险更常与高浓度沙奎那韦相关，但未确定阈值。几项研究（其中一项为随机研究）报告了沙奎那韦治疗药物监测对优化病毒学反应的益处。因此，沙奎那韦治疗药物监测益处的证据水平为“推荐”。
