洛匹那韦利托那韦联合基于利福平的抗结核治疗在感染 HIV 的南非儿童中的群体药代动力学。
Population pharmacokinetics of lopinavir in combination with rifampicin-based antitubercular treatment in HIV-infected South African children.
机构信息
Department of Pharmaceutical Biosciences, Uppsala University, Box 591, BMC, 751 24 Uppsala, Sweden.
出版信息
Eur J Clin Pharmacol. 2010 Oct;66(10):1017-23. doi: 10.1007/s00228-010-0847-9. Epub 2010 Jun 16.
PURPOSE
The population pharmacokinetics (PK) of lopinavir in tuberculosis (TB)/human immunodeficiency virus (HIV) co-infected South African children taking super-boosted lopinavir (lopinavir/ritonavir ratio 1:1) as part of antiretroviral treatment in the presence of rifampicin were compared with the population PK of lopinavir in HIV-infected South African children taking standard doses of lopinavir/ritonavir (ratio 4:1).
METHODS
Lopinavir concentrations were measured in 15 TB/HIV-co-infected paediatric patients who were sampled during and after rifampicin-based TB treatment and in 15 HIV-infected children without TB. During TB therapy, the dose of ritonavir was increased to lopinavir/ritonavir 1:1 in order to compensate for the induction of rifampicin. The children received median (interquartile range=IQR) doses of lopinavir 292 mg/m(2) (274, 309) and ritonavir 301 mg/m(2) (286, 309) twice daily. After TB treatment completion the children received standard doses of lopinavir/ritonavir 4:1 (median [IQR] lopinavir dose 289 mg/m(2) [286, 303] twice daily) as did those without TB (median [IQR] lopinavir dose 265 mg/m(2) [249, 289] twice daily).
RESULTS
Lopinavir oral clearance (CL/F) was about 30% lower in children without TB than in co-infected children treated with super-boosted lopinavir. However, the predicted lopinavir C(min) was above the recommended minimum therapeutic concentration during TB/HIV co-treatment in the 15 children. Lopinavir CL/F increased linearly during the dosing interval.
CONCLUSIONS
Increasing the ritonavir dose to achieve a lopinavir/ritonavir ratio of 1:1 when given in combination with rifampicin-based TB treatment did not completely compensate for the enhancement of lopinavir CL/F caused by rifampicin. The time-dependent lopinavir CL/F might be due to a time-dependent recovery from ritonavir inhibition of lopinavir metabolism during the dosing interval.
目的
在南非，肺结核（TB）/人类免疫缺陷病毒（HIV）合并感染的儿童在接受利福平为基础的结核病治疗时，接受超级强化洛匹那韦（洛匹那韦/利托那韦比例为 1:1）作为抗逆转录病毒治疗的一部分，其洛匹那韦的群体药代动力学（PK）与接受标准剂量洛匹那韦/利托那韦（比例为 4:1）的 HIV 感染南非儿童的洛匹那韦群体 PK 进行了比较。
方法
在 15 例接受利福平为基础的结核病治疗的 TB/HIV 合并感染的儿科患者和 15 例无结核病的 HIV 感染儿童中，检测了洛匹那韦的浓度。在结核病治疗期间，为了补偿利福平诱导，将利托那韦的剂量增加到洛匹那韦/利托那韦 1:1。这些儿童接受洛匹那韦 292mg/m²（274，309）和利托那韦 301mg/m²（286，309）每日两次的中位数（四分位间距=IQR）剂量。在结核病治疗完成后，这些儿童接受标准剂量的洛匹那韦/利托那韦 4:1（中位数[IQR]洛匹那韦剂量 289mg/m²[286，303]每日两次），无结核病的儿童也接受标准剂量的洛匹那韦/利托那韦 4:1（中位数[IQR]洛匹那韦剂量 265mg/m²[249，289]每日两次）。
结果
无结核病儿童的洛匹那韦口服清除率（CL/F）比接受超级强化洛匹那韦治疗的合并感染儿童低约 30%。然而，在 15 名儿童中，在 TB/HIV 合并治疗期间，预测的洛匹那韦 C（最小）高于推荐的最小治疗浓度。洛匹那韦 CL/F 在给药间隔内呈线性增加。
结论
当与利福平为基础的结核病治疗联合使用时，增加利托那韦剂量以达到洛匹那韦/利托那韦 1:1 的比例，并不能完全补偿利福平引起的洛匹那韦 CL/F 的增强。洛匹那韦 CL/F 的时变可能是由于在给药间隔内利托那韦抑制洛匹那韦代谢的时变恢复所致。
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