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首页> 美国卫生研究院文献>Antimicrobial Agents and Chemotherapy >Lack of a Clinically Important Effect of Moderate Hepatic Insufficiency and Severe Renal Insufficiency on Raltegravir Pharmacokinetics
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Lack of a Clinically Important Effect of Moderate Hepatic Insufficiency and Severe Renal Insufficiency on Raltegravir Pharmacokinetics

机译：中度肝功能不全和严重肾功能不全对Raltegravir药代动力学缺乏重要的临床意义

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Raltegravir is a human immunodeficiency virus type 1 integrase strand transfer inhibitor with potent activity in vitro and in vivo. Raltegravir is primarily cleared by hepatic metabolism via glucuronidation (via UDP glucuronosyltransferase 1A1), with a minor component of elimination occurring via the renal pathway. Since the potential exists for raltegravir to be administered to patients with hepatic or renal insufficiency, two studies were conducted to evaluate the influence of moderate hepatic insufficiency (assessed by using the Child-Pugh criteria) and severe renal insufficiency (creatinine clearance, <30 ml/min/1.73 m2) on the pharmacokinetics of raltegravir. Study I evaluated the pharmacokinetics of 400 mg raltegravir in eight patients with moderate hepatic insufficiency and eight healthy, matched control subjects. Study II evaluated the pharmacokinetics of 400 mg raltegravir in 10 patients with severe renal insufficiency and 10 healthy, matched control subjects. All participants received a single 400-mg dose of raltegravir in the fasted state. In study I, the geometric mean ratios (GMR; mean value for the group with moderate hepatic insufficiency/mean value for the healthy controls) and 90% confidence intervals (CIs) for the area under the concentration-time curve from time zero to infinity (AUC0-∞), the maximum concentration of drug in plasma (Cmax), and the concentration at 12 h (C12) were 0.86 (90% CI, 0.41, 1.77), 0.63 (90% CI, 0.23, 1.70), and 1.26 (90% CI, 0.65, 2.43), respectively. In study II, the GMRs (mean value for the group with renal insufficiency/mean value for the healthy controls) and 90% CIs for AUC0-∞, Cmax, and C12 were 0.85 (90% CI, 0.49, 1.49), 0.68 (90% CI, 0.35, 1.32), and 1.28 (90% CI, 0.79, 2.06), respectively. Raltegravir was generally well tolerated by patients with moderate hepatic or severe renal insufficiency, and there was no clinically important effect of moderate hepatic or severe renal insufficiency on the pharmacokinetics of raltegravir. No adjustment in the dose of raltegravir is required for patients with mild or moderate hepatic or renal insufficiency.
机译：Raltegravir是一种人类免疫缺陷病毒1型整合酶链转移抑制剂，在体外和体内均具有有效活性。 Raltegravir主要通过肝糖苷酸化（通过UDP葡萄糖醛酸糖基转移酶1A1）通过肝代谢清除，而微量的清除途径是通过肾脏途径进行的。由于存在可能将raltegravir应用于肝或肾功能不全的患者，因此进行了两项研究，以评估中度肝功能不全（使用Child-Pugh标准进行评估）和严重肾功能不全（肌酐清除率<30 ml）的影响/min/1.73 m 2 ）对拉格韦的药代动力学。研究一评估了400 mg raltegravir在8例中度肝功能不全患者和8例健康，匹配的对照受试者中的药代动力学。研究II评价了400 mg raltegravir在10例严重肾功能不全患者和10例健康，匹配的对照受试者中的药代动力学。在空腹状态下，所有参与者均接受了400 mg剂量的raltegravir。在研究I中，几何平均比率（GMR；中度肝功能不全/健康对照组平均值的组的平均值）和从时间零到无穷大的浓度-时间曲线下面积的90％置信区间（CIs） （AUC0-∞），血浆中最大药物浓度（Cmax）和12 h（C12）浓度分别为0.86（90％CI，0.41、1.77），0.63（90％CI，0.23、1.70）和分别为1.26（90％CI，0.65、2.43）。在研究II中，GMR（肾功能不全组的平均值/健康对照组的平均值）和AUC0-∞，Cmax和C12的90％CI为0.85（90％CI，0.49、1.49），0.68（ 90％CI，0.35、1.32）和1.28（90％CI，0.79、2.06）。中度肝或重度肾功能不全的患者通常对Raltegravir耐受良好，中度肝或重度肾功能不全对Raltegravir的药代动力学没有临床上重要的影响。轻度或中度肝或肾功能不全的患者无需调整raltegravir的剂量。

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