Peng Joanna Z, Pulido Federico, Causemaker Sonja J Kemmis, Li Jianling, Lorenzo Alicia, Cepeda Concepción, García Cabanillas Juan A, DaSilva Barbara, Brun Scott C, Arribas José
Abbott Laboratories, Clinical Pharmacology & Pharmacometrics (Department R4PK, Building AP13A-3), 100 Abbott Park Road, Abbott Park, IL 60064-6104, USA.
J Clin Pharmacol. 2006 Mar;46(3):265-74. doi: 10.1177/0091270005284853.
The effect of hepatic impairment on lopinavir/ritonavir pharmacokinetics was investigated. Twenty-four HIV-1-infected subjects received lopinavir 400 mg/ritonavir 100 mg twice daily prior to and during the study: 6 each with mild or moderate hepatic impairment (and hepatitis C virus coinfected) and 12 with normal hepatic function. Mild and moderate hepatic impairment showed similar effects on lopinavir pharmacokinetics. When the 2 hepatic impairment groups were combined, lopinavir Cmax and AUC12 were increased 20% to 30% compared to the controls. Hepatic impairment increased unbound lopinavir AUC12 by 68% and Cmax by 56%. The effect of hepatic impairment on low-dose ritonavir pharmacokinetics was more pronounced in the moderate impairment group (181% and 221% increase in AUC12 and Cmax, respectively) than in the mild impairment group (39% and 61% increase in AUC12 and Cmax, respectively). While lopinavir/ritonavir dose reduction is not recommended in subjects with mild or moderate hepatic impairment, caution should be exercised in this population.
研究了肝功能损害对洛匹那韦/利托那韦药代动力学的影响。24名感染HIV-1的受试者在研究前和研究期间每天两次接受400mg洛匹那韦/100mg利托那韦治疗：6名轻度或中度肝功能损害（合并丙型肝炎病毒感染）患者和12名肝功能正常患者。轻度和中度肝功能损害对洛匹那韦药代动力学的影响相似。当将两个肝功能损害组合并时，与对照组相比，洛匹那韦的Cmax和AUC12增加了20%至30%。肝功能损害使游离洛匹那韦的AUC12增加68%，Cmax增加56%。肝功能损害对低剂量利托那韦药代动力学的影响在中度损害组（AUC12和Cmax分别增加181%和221%）比轻度损害组（AUC12和Cmax分别增加39%和61%）更明显。虽然不建议对轻度或中度肝功能损害的患者降低洛匹那韦/利托那韦剂量，但对此类人群应谨慎用药。
