The effect of lopinavir/ritonavir on the renal clearance of tenofovir in HIV-infected patients

被引：168

作者：

Kiser, J. J. ^{[1
]}

Carten, M. L. ^{[2
]}

Aquilante, C. L. ^{[1
]}

Anderson, P. L. ^{[1
]}

Wolfe, P. ^{[3
]}

King, T. M. ^{[1
]}

Delahunty, T. ^{[1
]}

Bushman, L. R. ^{[1
]}

Fletcher, C. V. ^{[1
,2
]}

机构：

[1] Univ Colorado, Sch Pharm, Denver, CO 80262 USA

[2] Univ Colorado, Dept Med, Div Infect Dis, Boulder, CO 80309 USA

[3] Univ Colorado, Dept Prevent Med & Biometr, Denver, CO USA

来源：

CLINICAL PHARMACOLOGY & THERAPEUTICS | 2008年 / 83卷 / 02期

关键词：

D O I：

10.1038/sj.clpt.6100269

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

We determined the effects of lopinavir/ritonavir on tenofovir renal clearance. Human immunodeficiency virus-infected subjects taking tenofovir disoproxil fumarate (TDF) were matched on age, race, and gender and were enrolled into one of the following two groups: group 1: subjects taking TDF plus lopinavir/ritonavir plus other nucleoside reverse transcriptase inhibitors (NRTIs); group 2: subjects taking TDF plus NRTIs and/or non-NRTIs but no protease inhibitors. Twenty-four-hour blood and urine collections were carried out in subjects for tenofovir quantification. Drug transporter genotype associations with tenofovir pharmacokinetics were examined. In 30 subjects, median (range) tenofovir apparent oral clearance, renal clearance, and fraction excreted in urine were 34.6 l/h (20.6-89.5), 11.3 l/h (6.2-22.6), and 0.33 (0.23-0.5), respectively. After adjusting for renal function, tenofovir renal clearance was 17.5% slower (P=0.04) in subjects taking lopinavir/ritonavir versus those not taking a protease inhibitor, consistent with a renal interaction between these drugs. Future studies should clarify the exact mechanism and whether there is an increased risk of nephrotoxicity.

引用

页码：265 / 272

页数：8

共 31 条

[1] Pharmacogenetic characteristics of indinavir, zidovudine, and lamivudine therapy in HIV-infected adults: A pilot study [J].