当前位置: X-MOL 学术Ann. Clin. Microbiol. Antimicrob. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
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.
Annals of Clinical Microbiology and Antimicrobials ( IF 4.6 ) Pub Date : 2020-01-22 , DOI: 10.1186/s12941-020-0345-6
Henri Gautier Ouedraogo 1 , Alberto Matteelli 2 , Giorgia Sulis 3, 4 , Tegwinde Rebeca Compaore 1 , Serge Diagbouga 1 , Simon Tiendrebeogo 1 , Alberto Roggi 2 , Kadari Cisse 1 , Pier Francesco Giorgetti 5 , Paola Villani 5 , Lassana Sangare 6 , Jacques Simpore 7 , Mario Regazzi 5 , Seni Kouanda 1
Affiliation  

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 Cmax and Tmax were respectively, 20 μg/mL and 4 h for the RBT 150 mg group (arm A) and 7.7 μg/mL and 3 h for the RBT 300 mg group (arm B). The AUC0-12 of LPV was 111.8 μg h/mL in patients belonging to arm A versus 69.9 μg/mL for those in arm B (p = 0.313). The C0 of LPV was lower than 4 μg/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 AUC0-12 of RTV in arm A was 12.7 μg h/mL versus 6.6 μg 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/.

中文翻译:

血浆洛匹那韦和利托那韦在结核病-HIV合并感染的非洲成年患者中的药代动力学,每周也要接受150或300 mg利福布汀。

背景技术评估血浆洛匹那韦(LPV)和利托那韦(RTV)与每周三次(TPW)利福布汀(RBT)并用150或300 mg剂量在非洲结核病(TB)和HIV联合中的药代动力学受感染的成年患者。方法这是在瓦加杜古进行的一项药代动力学研究,接受标准剂量的LPV / RTV 400/100 mg每天两次和RBT 150 mg TPW(A组= 9名患者)或rifabutin 300 mg TPW(B组= 7名患者)治疗基础的方案。患者于2013年5月至2015年12月在瓦加杜古的Bogodogo和Kossodo地区医院招募。研究纳入标准为患者年龄在18至60岁之间,证实或怀疑患有肺结核的HIV-1。随后在1、2、3、4采集血样用于药代动力学监测 联合摄入药物后第6、8和12小时,使用HPLC / MS分析监测血浆药物。结果RBT 150 mg组(组A)的LPV Cmax和Tmax中位数分别为20μg/ mL和4 h,RBT 300 mg组(组B)的7.7μg/ mL和3 h。A组患者LPV的AUC0-12为111.8μgh / mL,而B组患者为69.9μg/ mL(p = 0.313)。在接受RBT 300 mg的三例患者中,LPV的C0低于4μg/ mL。值得注意的是,使用RBT 300 mg的患者与使用较低RBT剂量的患者相比,RTV血浆浓度几乎减少了一半。A组RTV的AUC0-12为12.7μgh / mL,而B组为6.6μgh / ml(p = 0.313)。结论在我们的研究中,发现LPV和RTV的药代动力学与每周150次或300毫克RBT并用时,变化很大。需要进行大量的具体研究,以验证这种变异的临床和病毒学效应,尤其是与300 mg TPW的RBT并用时,并防止对LPV剂量不足引起的病毒耐药性。试用注册PACTR201310000629390。于2013年10月28日注册,http://www.pactr.org/。
更新日期:2020-04-22
down
wechat
bug