Pharmacokinetics of plasma lopinavir and ritonavir in tuberculosis-HIV co-infected African adult patients also receiving rifabutin 150 or 300 mg three times per week
Pharmacokinetics of plasma lopinavir and ritonavir in tuberculosis-HIV co-infected African adult patients also receiving rifabutin 150 or 300 mg three times per week
复制标题
DOI：
10.1186/s12941-020-0345-6
复制
发表时间：
2020-01-22
影响因子：
5.7
通讯作者：
Kouanda, Seni
中科院分区：
文献类型：
--
作者：
Ouedraogo, Henri Gautier;Matteelli, Alberto;Kouanda, Seni
目的：评价非洲结核病（TB）和HIV合并感染的成人患者中，每周三次（TPW）利福伯胺（RBT）以150或300 mg剂量联合给药时，血浆洛匹那韦（LPV）和利托那韦（RTV）的药代动力学。方法本研究在瓦加杜古进行，在接受标准剂量LPV/RTV 400/100 mg每日2次和RBT 150 mg TPW（A组= 9例患者）或利福朋300 mg TPW（B组= 7例患者）治疗的患者中进行药代动力学研究。患者于2013年5月至2015年12月从瓦加杜古的Bogodogo和Kossodo地区医院招募。研究入选标准为患者年龄在18 ~ 60岁之间，HIV-1感染确诊或疑似肺结核。随后在联合药物摄入后1、2、3、4、6、8和12 h采集用于药代动力学监测的血样，使用HPLC/MS测定法进行血浆药物监测。结果RBT 150 mg组（A组）的中位LPV C-max和Tmax分别为20 μ g/mL和4 h; RBT 300 mg组（B组）的中位LPV C-max和Tmax分别为7.7 μ g/mL和3 h。A组患者的LPV AUC（0-12）为111.8 μ g h/mL，而B组患者为69.9 μ g/mL（p = 0.313）。3例接受RBT 300 mg的患者LPV的C-0低于4 μ g/mL。值得注意的是，与接受较低RBT剂量的患者相比，接受RBT 300 mg的患者的RTV血浆浓度几乎减半。A组RTV的AUC（0-12）为12.7 μ g h/mL，而B组为6.6 μ g h/mL（p = 0.313）。结论RBT 150 mg或300 mg每周3次与LPV和RTV合用时，LPV和RTV的药代动力学具有高度变异性。需要进行特定的大型研究，以验证这种变化的临床和病毒学影响，特别是当与300 mg TPW的RBT联合给药时，并防止LPV剂量不足引起的病毒耐药性。试验注册PACTR 201310000629390。2013年10月28日注册，http://www.pactr.org/
Background To evaluate the pharmacokinetic of plasma lopinavir (LPV) and ritonavir (RTV) when co-administered with three times weekly (TPW) rifabutin (RBT) at a dose of either 150 or 300 mg in African tuberculosis (TB) and HIV co-infected adult patients. Methods This is a pharmacokinetic study conducted in Ouagadougou among patients treated with a standard dosage of LPV/RTV 400/100 mg twice daily and RBT 150 mg TPW (arm A = 9 patients) or rifabutin 300 mg TPW (arm B = 7 patients) based regimens. Patients were recruited from the Bogodogo and Kossodo district hospitals in Ouagadougou from May 2013 to December 2015. Study inclusion criteria were that the patients were between 18 and 60 years of age, HIV-1 infected with pulmonary tuberculosis confirmed or suspected. Subsequent blood samples for pharmacokinetic monitoring were collected at 1, 2, 3, 4, 6, 8 and 12 h after combined drug ingestion for plasma drug monitoring using HPLC/MS assays. Results The medians LPV C-max and T-max were respectively, 20 mu g/mL and 4 h for the RBT 150 mg group (arm A) and 7.7 mu g/mL and 3 h for the RBT 300 mg group (arm B). The AUC(0-12) of LPV was 111.8 mu g h/mL in patients belonging to arm A versus 69.9 mu g/mL for those in arm B (p = 0.313). The C-0 of LPV was lower than 4 mu g/mL in three patients receiving RBT 300 mg. Of note, the RTV plasma concentrations were nearly halved among patients on RBT 300 mg compared to those on lower RBT doses. The AUC(0-12) of RTV in arm A was 12.7 mu g h/mL versus 6.6 mu g h/ml in arm B (p = 0.313). Conclusion In our study, the pharmacokinetic of LPV and RTV was found to be highly variable when coadministrated with RBT 150 mg or 300 mg three times per week. There is a need for specific large study to verify clinical and virological effects of this variation, especially when coadministrated with RBT of 300 mg TPW, and to prevent viral resistance in response to under-dosing of LPV. Trial registration PACTR201310000629390. Registered 28 October 2013, http://www.pactr.org/