University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands.
University of Groningen, University Medical Center Groningen, Department of Internal Medicine - Infectious Diseases, Groningen, The Netherlands.
Br J Clin Pharmacol. 2018 Mar;84(3):456-461. doi: 10.1111/bcp.13464. Epub 2017 Dec 7.
Darunavir is an efficacious drug; however, pharmacokinetic variability has been reported. The objective of this study was to find predisposing factors for low darunavir plasma concentrations in patients starting the once- or twice-daily dosage. Darunavir plasma concentrations from January 2010 till December 2014 of human immunodeficiency virus-infected individuals treated in the outpatient clinic of the University Medical Center Groningen were retrospectively reviewed. The first darunavir plasma concentration of patients within 8 weeks after initiation of darunavir therapy was selected. A dichotomous logistic regression analysis was conducted to select the set of variables best predicting a darunavir concentration below median population pharmacokinetic curve. In total 113 patients were included. The variables best predicting a darunavir concentration besides food intake included age together with estimated glomerular filtration rate (Hosmer-Lemeshow test P = 0.945, Nagelkerke R = 0.284). Systematic evaluation of therapeutic drug monitoring results may help to identify patients at risk for low drug exposure.
达芦那韦是一种有效的药物；然而，已有报道称其药代动力学存在变异性。本研究的目的是寻找开始接受每日一次或两次剂量治疗的患者中达芦那韦血浆浓度低的易感因素。回顾性分析了 2010 年 1 月至 2014 年 12 月在格罗宁根大学医学中心门诊治疗的人类免疫缺陷病毒感染患者的达芦那韦血浆浓度。选择达芦那韦治疗开始后 8 周内患者的第一个达芦那韦血浆浓度。进行二项逻辑回归分析，以选择一组最佳预测达芦那韦浓度低于人群药代动力学曲线中位数的变量。共纳入 113 例患者。除了饮食摄入外，能最好预测达芦那韦浓度的变量包括年龄和估计肾小球滤过率（Hosmer-Lemeshow 检验 P=0.945，Nagelkerke R=0.284）。对治疗药物监测结果进行系统评估可能有助于识别药物暴露不足的风险患者。
