Pharmacokinetics of antiretroviral regimens containing tenofovir disoproxil fumarate and atazanavir-ritonavir in adolescents and young adults with human immunodeficiency virus infection
Pharmacokinetics of antiretroviral regimens containing tenofovir disoproxil fumarate and atazanavir-ritonavir in adolescents and young adults with human immunodeficiency virus infection
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DOI：
10.1128/aac.00761-07
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发表时间：
2008-02-01
影响因子：
4.9
通讯作者：
Havens, Peter L.
中科院分区：
文献类型：
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作者：
Kiser, Jennifer J.;Fletcher, Courtney V.;Havens, Peter L.
本研究的主要目的是测量阿扎那韦-利托那韦和替诺福韦在年轻成人人类免疫缺陷病毒（HIV）联合使用时的药代动力学。hiv感染者（bb0 = 18 ~ = 28天）300/100 mg阿扎那韦-利托那韦加300 mg富马酸替诺福韦二氧吡酯（TDF）加一种或多种其他核苷类似物，在餐后24小时进行强化药代动力学研究。在给药后1、4和24小时取外周血单个核细胞，定量细胞内二磷酸替诺福韦（TFV-DP）浓度。22名受试者符合分析条件。阿扎那韦0 ~ 24 h浓度-时间曲线下的几何平均（95%可信区间[CI]）面积（AUC(0 ~ 24)）、血清中最大药物浓度（C-max）、给药后24 h浓度（C-24）和总表观口服清除率（CL/F）分别为35971 ng中心点hr/ml（30853 ~ 41898）、3504 ng/ml（2978 ~ 4105）、578 ng/ml（474 ~ 704）和8.3 l /hr（7.2 ~ 9.7）。几何平均（95% Cl）替诺福韦AUC（0 ~ 24）、C-max C-24和Cl /F值分别为2,762 ng中心点hr/ml（2,392 ~ 3,041）、254 ng/ml（221 ~ 292）、60 ng/ml（52 ~ 68）和49.2 l /hr（43.8 ~ 55.3）。体重可显著预测三种药物的CL/F。体重每增加10公斤，阿扎那韦、利托那韦和替诺福韦CL/F分别增加10%、14.8%和6.8% (P
The primary objective of this study was to measure atazanavir-ritonavir and tenofovir pharmacokinetics when the drugs were used in combination in young adults with human immunodeficiency virus (HIV). HIV-infected subjects >= 18 to = 28 days) 300/100 mg atazanavir-ritonavir plus 300 mg tenofovir disoproxil fumarate (TDF) plus one or more other nucleoside analogs underwent intensive 24-h pharmacokinetic studies following a light meal. Peripheral blood mononuclear cells were obtained at 1, 4, and 24 h postdose for quantification of intracellular tenofovir diphosphate (TFV-DP) concentrations. Twenty-two subjects were eligible for analyses. The geometric mean (95% confidence interval [CI]) atazanavir area under the concentration-time curve from 0 to 24 h (AUC(0-24)), maximum concentration of drug in serum (C-max), concentration at 24 h postdose (C-24), and total apparent oral clearance (CL/F) values were 35,971 ng center dot hr/ml (30,853 to 41,898), 3,504 ng/ml (2,978 to 4,105), 578 ng/ml (474 to 704), and 8.3 liter/hr (7.2 to 9.7), respectively. The geometric mean (95% Cl) tenofovir AUC(0-24), C-max C-24, and CL/F values were 2,762 ng center dot hr/ml (2,392 to 3,041), 254 ng/ml (221 to 292), 60 ng/ml (52 to 68), and 49.2 liter/hr (43.8 to 55.3), respectively. Body weight was significantly predictive of CL/F for all three drugs. For every 10-kg increase in weight, there was a 10%, 14.8%, and 6.8% increase in the atazanavir, ritonavir, and tenofovir CL/F, respectively (P