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

J. J. Kiser, M. L. Carten, C. L. Aquilante, P. L. Anderson, P. Wolfe, T. M. King, T. Delahunty, L. R. Bushman, C. V. Fletcher

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)265-272
Number of pages8
JournalClinical Pharmacology and Therapeutics
Volume83
Issue number2
DOIs
StatePublished - Feb 1 2008

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Tenofovir
Lopinavir
Ritonavir
HIV
Kidney
Reverse Transcriptase Inhibitors
Protease Inhibitors
Nucleosides
Urine Specimen Collection
Drug Interactions

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

The effect of lopinavir/ritonavir on the renal clearance of tenofovir in HIV-infected patients. / Kiser, J. J.; Carten, M. L.; Aquilante, C. L.; Anderson, P. L.; Wolfe, P.; King, T. M.; Delahunty, T.; Bushman, L. R.; Fletcher, C. V.

In: Clinical Pharmacology and Therapeutics, Vol. 83, No. 2, 01.02.2008, p. 265-272.

Research output: Contribution to journalArticle

Kiser, JJ, Carten, ML, Aquilante, CL, Anderson, PL, Wolfe, P, King, TM, Delahunty, T, Bushman, LR & Fletcher, CV 2008, 'The effect of lopinavir/ritonavir on the renal clearance of tenofovir in HIV-infected patients', Clinical Pharmacology and Therapeutics, vol. 83, no. 2, pp. 265-272. https://doi.org/10.1038/sj.clpt.6100269
Kiser, J. J. ; Carten, M. L. ; Aquilante, C. L. ; Anderson, P. L. ; Wolfe, P. ; King, T. M. ; Delahunty, T. ; Bushman, L. R. ; Fletcher, C. V. / The effect of lopinavir/ritonavir on the renal clearance of tenofovir in HIV-infected patients. In: Clinical Pharmacology and Therapeutics. 2008 ; Vol. 83, No. 2. pp. 265-272.
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