Yeh K C, Deutsch P J, Haddix H, Hesney M, Hoagland V, Ju W D, Justice S J, Osborne B, Sterrett A T, Stone J A, Woolf E, Waldman S
Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
Antimicrob Agents Chemother. 1998 Feb;42(2):332-8. doi: 10.1128/AAC.42.2.332.
Indinavir sulfate is a human immunodeficiency virus type 1 (HIV-1) protease inhibitor indicated for treatment of HIV infection and AIDS in adults. The purpose of this report is to summarize single-dose studies which characterized the pharmacokinetics of the drug and the effect of food in healthy volunteers. Indinavir concentrations in plasma and urine were obtained by high-pressure liquid chromatography and UV detection assay methods. The results indicate that indinavir was rapidly absorbed in the fasting state, with the time to the maximum concentration in plasma occurring at approximately 0.8 h for all doses studied. Over the 40- to 1,000-mg dose range studied, concentrations in plasma and urinary excretion of unchanged drug increased greater than dose proportionally. The nonlinear pharmacokinetics were attributed to the dose-dependent oxidative metabolism of first-pass metabolism as well as to metabolism in the systemic circulation. Renal clearance slightly exceeded the glomerular filtration rate, suggesting a net tubular secretion component. At high concentrations in plasma, tubular secretion appeared to be lowered because there was a trend for a decreased renal clearance. Administration of 400 mg of indinavir sulfate following a high-fat breakfast resulted in a blunted and decreased absorption (areas under the concentration-time curves [AUCs], 6.86 microM.h in the fasted state versus 1.54 microM.h in the fed state; n = 10). However, two types of low-fat meals were found to have no significant effect on the absorption of 800 mg of indinavir sulfate (AUCs, 23.15 microM.h in the fasted state versus 22.71 and 21.36 microM.h, respectively, in the fed state; n = 11). Immediately following dosing, the concentrations of indinavir in urine often exceeded its intrinsic solubility. To reduce the risk of nephrolithiasis, it is recommended that indinavir sulfate be administered with water.
硫酸茚地那韦是一种1型人类免疫缺陷病毒（HIV-1）蛋白酶抑制剂，适用于治疗成人HIV感染和艾滋病。本报告的目的是总结单剂量研究，这些研究描述了该药物在健康志愿者中的药代动力学及食物的影响。通过高压液相色谱法和紫外检测分析方法测定血浆和尿液中的茚地那韦浓度。结果表明，茚地那韦在禁食状态下吸收迅速，在所研究的所有剂量下，血浆中达到最大浓度的时间约为0.8小时。在所研究的4至1000毫克剂量范围内，血浆浓度和未变化药物的尿排泄量增加幅度大于剂量比例。非线性药代动力学归因于首过代谢的剂量依赖性氧化代谢以及体循环中的代谢。肾清除率略超过肾小球滤过率，提示存在肾小管分泌成分。在血浆高浓度时，肾小管分泌似乎降低，因为肾清除率有下降趋势。高脂早餐后服用400毫克硫酸茚地那韦导致吸收减弱和减少（浓度-时间曲线下面积[AUC]，禁食状态下为6.86微摩尔·小时，进食状态下为1.54微摩尔·小时；n = 10）。然而，发现两种低脂餐对800毫克硫酸茚地那韦的吸收无显著影响（AUC，禁食状态下为23.15微摩尔·小时，进食状态下分别为22.71和21.36微摩尔·小时；n = 11）。给药后即刻，尿液中茚地那韦的浓度常常超过其固有溶解度。为降低肾结石风险，建议硫酸茚地那韦与水一起服用。
