Pharmacokinetics of Lopinavir in HIV-Infected Adults Receiving Rifampin with Adjusted Doses of Lopinavir-Ritonavir Tablets
Pharmacokinetics of Lopinavir in HIV-Infected Adults Receiving Rifampin with Adjusted Doses of Lopinavir-Ritonavir Tablets
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DOI：
10.1128/aac.01598-10
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发表时间：
2011-07-01
影响因子：
4.9
通讯作者：
Maartens, Gary
中科院分区：
文献类型：
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作者：
Decloedt, Eric H.;McIlleron, Helen;Maartens, Gary
利福平联合用药可显著降低血浆洛匹那韦（LPV）浓度。在健康志愿者中，双倍剂量的洛匹那韦-利托那韦（LPV/r）胶囊配方克服了这种相互作用，但随后的双倍剂量片剂配方的研究由于肝毒性而提前停止。然而，健康志愿者的研究结果可能不适用于感染艾滋病毒的成年人。我们评估了LPV/r方案下给予利福平的hiv感染成人病毒学抑制的LPV的稳态药代动力学，并逐渐增加LPV/r片剂的剂量。在基线、开始使用利福平1周、LPV/r剂量增加1.5倍后1周、LPV/r剂量加倍后1周评估LPV/r的稳态药代动力学。21名参与者被招募。给药前LPV浓度（c0）的中位数[四分位数范围（IQR）]基线时为8.1(6.2至9.8)mg/l，利福平7天后为1.7(0.3至3.0)mg/l， 1.5倍LPV/r剂量组为5.9(2.1至9.9)mg/l，双剂量LPV/r组为10.8(7.0至13.1)mg/l。基线与双剂量LPV/r时间点在0 ~ 12 h血浆浓度-时间曲线下的LPV面积（AUC0-12）、c0、c12、血清中最大药物浓度（C-max）、半衰期（t(1/2)）无显著差异。治疗总体耐受良好，两名参与者发展为无症状的3/4级转氨炎。双倍剂量的LPV/r片剂配方克服了利福平诱导。在我们的hiv感染者队列中发生的肝毒性比在健康志愿者研究中报道的要少。
Rifampin coadministration dramatically reduces plasma lopinavir (LPV) concentrations. In healthy volunteers, doubling the dose of a lopinavir-ritonavir (LPV/r) capsule formulation overcame this interaction, but a subsequent study of double doses of the tablet formulation was stopped early owing to hepatotoxicity. However, healthy-volunteer study findings may not apply to HIV-infected adults. We evaluated the steady-state pharmacokinetics of LPV in HIV-infected adults virologically suppressed on an LPV/r regimen who were given rifampin, and the dose of the LPV/r tablet formulation was gradually increased. The steady-state pharmacokinetics of LPV/r were evaluated at baseline, a week after commencing rifampin, a week after the LPV/r dose was increased 1.5 times, and a week after the LPV/r dose was doubled. Twenty-one participants were enrolled. The median [interquartile range (IQR)] predose LPV concentrations (C 0) were 8.1 (6.2 to 9.8) mg/liter at baseline, 1.7 (0.3 to 3.0) mg/liter after 7 days of rifampin, 5.9 (2.1 to 9.9) mg/liter with 1.5 times the dose of LPV/r, and 10.8 (7.0 to 13.1) mg/liter with double-dose LPV/r. There were no significant differences in the LPV area under the plasma concentration-time curve from 0 to 12 h (AUC0-12), C 0, C 12, maximum concentration of drug in serum (C-max), or half-life (t(1/2)) between the baseline and double-dose LPV/r time points. Treatment was generally well tolerated, with two participants developing asymptomatic grade 3/4 transaminitis. Doubling the dose of the tablet formulation of LPV/r overcomes induction by rifampin. Less hepatotoxicity occurred in our cohort of HIV-infected participants than was reported in healthy-volunteer studies.