Population pharmacokinetics of atazanavir/ritonavir in HIV-1-infected children and adolescents

被引：11

作者：

Foissac, Frantz ^{[1
,2
]}

Blanche, Stephane ^{[1
,3
]}

Dollfus, Catherine ^{[4
]}

Hirt, Deborah ^{[1
,2
]}

Firtion, Ghislaine ^{[5
]}

Laurent, Corinne ^{[6
]}

Treluyer, Jean-Marc ^{[1
,2
,7
,8
]}

Urien, Saik ^{[1
,2
,7
]}

机构：

[1] Univ Paris 05, EA 3620, Paris, France

[2] Hop Paris, AP HP, Clin Paris Ctr, Unite Rech, Paris, France

[3] Hop Necker Enfants Malad, AP HP, Unite Immunol Hematotol, Paris, France

[4] Hop Trousseau, AP HP, Serv Hematol & Oncol Pediat, F-75571 Paris, France

[5] Grp Hosp CHU Cochin, AP HP, F-75571 Paris, France

[6] Hop Louis Mourier, AP HP, Serv Pediat & Neonatol, Paris, France

[7] INSERM, CIC 0901, Paris, France

[8] Hop St Vincent de Paul, Pharmacol Lab, F-75674 Paris, France

来源：

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY | 2011年 / 72卷 / 06期

关键词：

atazanavir; children; population pharmacokinetics; ritonavir; STEADY-STATE PHARMACOKINETICS; UNBOOSTED ATAZANAVIR; BOOSTED ATAZANAVIR; COMBINATION; RITONAVIR; EFFICACY; SAFETY;

D O I：

10.1111/j.1365-2125.2011.04035.x

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

AIMS To investigate atazanavir (ATV) population pharmacokinetics in children and adolescents, establish factors that influence ATV pharmacokinetics and investigate the ATV exposure after recommended doses. METHODS Atazanavir concentrations were measured in 51 children/adolescents during a mean therapeutic monitoring follow up of 6.6 months. A total of 151 ATV plasma concentrations were obtained, and a population pharmacokinetic model was developed with NONMEM. Patients received ATV alone or boosted with ritonavir. RESULTS Atazanavir pharmacokinetics was best described by a one-compartment model with first-order absorption and elimination. The effect of bodyweight was added on both apparent elimination clearance (CL/F) and volume of distribution using allometric scaling. Atazanavir CL/F was reduced by ritonavir by 45%. Tenofovir disoproxil fumarate (TDF) co-medication (300 mg) increased significantly by 25% the atazanavir/ritonavir (ATV/r) CL/F. Mean ATV/r CL/F values with or without TDF were 8.9 and 7.1 L h(-1) (70 kg)(-1), respectively. With the recommended 250/100 mg and 300/100 mg ATV/r doses, the exposure was higher than the mean adult steady-state exposure in the bodyweight range of 32-50 kg. CONCLUSIONS To target the mean adult exposure, children should receive the following once-daily ATV/r dose: 200/100 mg from 25 to 39 kg, 250/100 mg from 39 to 50 kg and 300/100 mg above 50 kg. When 300 mg TDF is co-administered, children should receive (ATV/r) at 250/100 mg between 35 and 39 kg, then 300/100 mg over 39 kg.

引用

页码：940 / 947

页数：8

共 34 条

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