Aarnoutse Rob E, Wasmuth Jan-Christian, Fätkenheuer Gerd, Schneider Katrin, Schmitz Karina, de Boo Theo M, Reiss Peter, Hekster Yechiel A, Burger David M, Rockstroh Jürgen K
Department of Clinical Pharmacy, University Medical Centre Nijmegen, The Netherlands.
Antivir Ther. 2003 Aug;8(4):309-14.
The objective of this study was to compare indinavir peak plasma (Cmax) values after administration of indinavir/ritonavir 800/100 mg on an empty stomach or with food. High indinavir Cmax values have been associated with indinavir-related nephrotoxicity.
This was an open-label, randomized, two-treatment, two-period, cross-over pharmacokinetic study performed at steady state. HIV-infected patients who had been using indinavir/ritonavir 800/100 mg twice daily for at least 4 weeks were randomized to take this combination with a light breakfast (two filled rolls and 130 ml of fluid) on a first study day, and without food on a second day, or in the reverse order. The pharmacokinetics of indinavir and ritonavir were assessed after plasma and urine sampling during 12 h.
Data for nine patients were evaluated. Administration of indinavir/ritonavir 800/100 mg on an empty stomach resulted in a higher indinavir Cmax [geometric mean (GM) ratio - fasting/fed and 95% confidence interval (CI): 1.28 (1.08-1.52), P=0.01] and a trend to a shorter indinavir tmax (P=0.07) compared to administration with food. The mode of administration of indinavir/ritonavir did not affect plasma indinavir Cmax and AUC values, parameters that have been associated with the antiviral efficacy of indinavir, nor the urinary excretion of indinavir.
Administration of indinavir/ritonavir 800/100 mg on an empty stomach results in a higher indinavir Cmax compared to ingestion with a light meal. Stated the other way round, intake with a light meal reduces indinavir Cmax, which probably reflects a food-induced delay in the absorption of indinavir. It is recommended to administer indinavir/ritonavir 800/100 mg with food, as a possible means to prevent indinavir-related nephrotoxicity in patients who start or continue with this regimen.
本研究的目的是比较空腹或与食物同服茚地那韦/利托那韦800/100毫克后茚地那韦的血浆峰浓度（Cmax）值。茚地那韦的高Cmax值与茚地那韦相关的肾毒性有关。
这是一项在稳态下进行的开放标签、随机、双治疗、双周期、交叉药代动力学研究。将至少4周以来每天两次使用茚地那韦/利托那韦800/100毫克的HIV感染患者随机分为两组，在第一个研究日，一组在服用该组合药物时搭配一份清淡早餐（两个夹心面包卷和130毫升液体），另一组则空腹服用，第二天两组服用顺序颠倒。在12小时内采集血浆和尿液样本后评估茚地那韦和利托那韦的药代动力学。
对9名患者的数据进行了评估。与和食物同服相比，空腹服用茚地那韦/利托那韦800/100毫克导致茚地那韦Cmax更高[几何均值（GM）比 - 空腹/进食及95%置信区间（CI）：1.28（1.08 - 1.52），P = 0.01]，且茚地那韦达峰时间有缩短趋势（P = 0.07）。茚地那韦/利托那韦的给药方式不影响血浆茚地那韦Cmax和AUC值（这些参数与茚地那韦的抗病毒疗效相关），也不影响茚地那韦的尿排泄。
与清淡饮食同服相比，空腹服用茚地那韦/利托那韦800/100毫克会导致茚地那韦Cmax更高。反之，清淡饮食时服用会降低茚地那韦Cmax，这可能反映了食物导致茚地那韦吸收延迟。建议在开始或继续该治疗方案的患者中，与食物同服茚地那韦/利托那韦800/100毫克，作为预防茚地那韦相关肾毒性的一种可能方法。
