Tibotec Inc., Yardley, Pa., USA. vsekar @ tibus.jnj.com
Intervirology. 2010;53(3):176-82. doi: 10.1159/000289341. Epub 2010 Mar 3.
To investigate the potential for a pharmacokinetic interaction between darunavir (DRV, TMC114, Prezista), indinavir (IDV, Crixivan) and low-dose ritonavir (RTV, Norvir).
In three 7-day sessions, 17 HIV-negative healthy volunteers received treatment A (DRV/r 400/100 mg b.i.d.), treatment B (IDV/r 800/100 mg b.i.d.) and treatment C (DRV/r 400/100 mg b.i.d. + IDV 800 mg b.i.d.). On day 7, full pharmacokinetic profiles of DRV, IDV and RTV were determined. Safety and tolerability were also assessed.
Based on the least-squares means ratios, the steady-state exposure (area under the curve, AUC(12h)) and plasma concentrations (C(min) and C(max)) of IDV were increased by 23, 125 and 8%, respectively, when DRV was co-administered. The co-administration of IDV with DRV/r resulted in increases of 24, 44 and 11% for, respectively, DRV AUC(12h), C(min) and C(max), compared with administration of DRV/r alone. Eight volunteers discontinued due to an adverse event. Overall, adverse events and laboratory abnormalities were more commonly reported during treatments including IDV.
When used in combination with DRV/r, dose adjustment of IDV from 800 mg b.i.d. to 600 mg b.i.d. may be warranted in cases of intolerance.
研究达芦那韦（DRV，TMC114，普泽力）、茚地那韦（IDV，克力芝）和低剂量利托那韦（RTV，诺维乐）联合应用的药代动力学相互作用的可能性。
在三个为期 7 天的疗程中，17 名 HIV 阴性健康志愿者分别接受了以下三种治疗方案：治疗 A（DRV/r400/100mg 每日两次）、治疗 B（IDV/r800/100mg 每日两次）和治疗 C（DRV/r400/100mg 每日两次+IDV800mg 每日两次）。在第 7 天，对 DRV、IDV 和 RTV 的全药代动力学特征进行了测定。同时评估了安全性和耐受性。
基于最小二乘均数比值，当 DRV 与 IDV 合用时，IDV 的稳态暴露量（AUC(12h)）和血药浓度（C(min)和 C(max)）分别增加了 23%、125%和 8%。与单独使用 DRV/r 相比，当 DRV/r 与 IDV 合用时，DRV 的 AUC(12h)、C(min)和 C(max)分别增加了 24%、44%和 11%。有 8 名志愿者因不良反应而停药。总体而言，在包含 IDV 的治疗方案中，不良反应和实验室异常更为常见。
当与 DRV/r 联合使用时，如果不耐受，可能需要将 IDV 的剂量从 800mg 每日两次调整为 600mg 每日两次。
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