Factors associated with variability in rifampin plasma pharmacokinetics and the relationship between rifampin concentrations and induction of efavirenz clearance.
Factors associated with variability in rifampin plasma pharmacokinetics and the relationship between rifampin concentrations and induction of efavirenz clearance.
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DOI：
10.1002/phar.1388
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发表时间：
2014-03
期刊：
影响因子：
4.1
通讯作者：
Peloquin, Charles A.
中科院分区：
文献类型：
--
作者：
Kwara, Awewura;Cao, Lei;Yang, Hongmei;Poethke, Pamela;Kurpewski, Jaclynn;Tashima, Karen T.;Mahjoub, Behrang D.;Court, Michael H.;Peloquin, Charles A.
探讨利福平血浆药代动力学变异性的相关因素，探讨利福平药代动力学与利福平共给药时依非韦伦血浆药代动力学变化的关系。在这项随机交叉研究中，12名健康志愿者接受了600毫克/天的依非韦伦或600毫克依非韦伦与600毫克/天的利福平，持续8天。在至少2周的洗脱期后，受试者转入8天的替代方案。在每个研究周期的第8天采集样本进行药代动力学评估。采用高效液相色谱法测定药物浓度。采用非区室分析计算药代动力学参数。采用多因素分析检查与利福平药代动力学相关的因素。采用Spearman相关分析探讨利福平药代动力学与同用利福平时依非韦伦血浆药代动力学变化的关系。在11名可评估受试者中，利福平Cmax、AUC0-24h和体重归一化清除率的中位数四分位数范围（IQR）分别为8.9 (7.3-13.8)μg/mL、48.8 (29.6-67.4)μg·hr/mL和0.19 (0.11-0.29)L/hr/kg。SLCO1B1c。388A→G和SLCO1B1c。463C→A多态性共同影响利福平Cmax （R2=0.75）。男性和SLCO1B1c。463C→多态性共同影响利福平AUC0-24h （R2=0.52）和体重归一化清除率（R2=0.65）。4例利福平Cmax < 8 μg/mL（正常范围下端）患者均为c.463CA基因型。存在和不存在利福平时，利福平Cmax和AUC0-24h与依非韦伦AUC0-24h比值或体重归一化清除率无显著关系（P < 0.05）。患有SLCO1B1c的男性。463CA基因型患者利福平血浆暴露水平较低的风险增加。然而，血浆利福平浓度与共同给药期间利福平诱导依非韦伦清除的程度无关。
To identify factors associated with variability in rifampin plasma pharmacokinetics and explore the relationship between rifampin pharmacokinetics and change in efavirenz plasma pharmacokinetics with rifampin coadministration. In this randomized, cross-over study, 12 healthy volunteers received either efavirenz 600 mg/day or efavirenz 600 mg with rifampin 600 mg/day for 8 days. After a washout period of at least 2 weeks, subjects crossed over to the alternate 8-day regimen. Samples were obtained for pharmacokinetic assessment on day 8 of each study cycle. Drugs concentrations were determined by a validated HPLC. Pharmacokinetic parameters were calculated using noncompartmental analysis. Multivariate analysis was used to examine factors associated with rifampin pharmacokinetics. Spearman correlation analysis was used to investigate relationship between rifampin pharmacokinetics and change in efavirenz plasma pharmacokinetics with rifampin coadministration. Of 11 evaluable subjects, the median interquartile range (IQR) rifampin Cmax, AUC0-24h, and weight-normalized clearance were 8.9 (7.3-13.8) μg/mL, 48.8 (29.6-67.4) μg•hr/mL, and 0.19 (0.11-0.29) L/hr/kg, respectively. SLCO1B1c.388A→G and SLCO1B1c.463C→A polymorphisms jointly had significant effect on rifampin Cmax (R2=0.75). Male sex and SLCO1B1c.463C→A polymorphism together influenced rifampin AUC0-24h (R2=0.52) and weight-normalized clearance (R2=0.65). All four subjects with rifampin Cmax < 8 μg/mL (lower end of the normal range) had c.463CA genotype. Rifampin Cmax and AUC0-24h had no significant relationship with the efavirenz AUC0-24h ratio or weight-normalized clearance ratio in the presence versus absence of rifampin (P>0.05). Males with the SLCO1B1c.463CA genotype are at increased risk of lower rifampin plasma exposure. However, plasma rifampin concentrations did not correlate with the extent of induction of efavirenz clearance by rifampin during coadministration.
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DOI：
10.1056/nejmoa1013607
发表时间：
2011-10-20
期刊：
The New England journal of medicine
影响因子：
--
作者：
Havlir DV;Kendall MA;Ive P;Kumwenda J;Swindells S;Qasba SS;Luetkemeyer AF;Hogg E;Rooney JF;Wu X;Hosseinipour MC;Lalloo U;Veloso VG;Some FF;Kumarasamy N;Padayatchi N;Santos BR;Reid S;Hakim J;Mohapi L;Mugyenyi P;Sanchez J;Lama JR;Pape JW;Sanchez A;Asmelash A;Moko E;Sawe F;Andersen J;Sanne I;AIDS Clinical Trials Group Study A5221
通讯作者：
AIDS Clinical Trials Group Study A5221
DOI：
10.1214/10-aoas388
发表时间：
2011-01-01
期刊：
The annals of applied statistics
影响因子：
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作者：
Breheny P;Huang J
通讯作者：
Huang J
DOI：
10.1164/rccm.200605-637oc
发表时间：
2006-11-15
影响因子：
24.7
作者：
Chang, Kwok C.;Leung, Chi C.;Tam, Cheuk M.
通讯作者：
Tam, Cheuk M.
影响因子：
9.8
作者：
Schaid, Daniel J.;Batzler, Anthony J.;Hildebrandt, Michelle A. T.
通讯作者：
Hildebrandt, Michelle A. T.
DOI：
10.1056/nejmoa1013911
发表时间：
2011-10-20
期刊：
The New England journal of medicine
影响因子：
--
作者：
Blanc FX;Sok T;Laureillard D;Borand L;Rekacewicz C;Nerrienet E;Madec Y;Marcy O;Chan S;Prak N;Kim C;Lak KK;Hak C;Dim B;Sin CI;Sun S;Guillard B;Sar B;Vong S;Fernandez M;Fox L;Delfraissy JF;Goldfeld AE;CAMELIA (ANRS 1295–CIPRA KH001) Study Team
通讯作者：
CAMELIA (ANRS 1295–CIPRA KH001) Study Team