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.
Publication types
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Clinical Trial
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenine / administration & dosage
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Adenine / analogs & derivatives*
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Adenine / pharmacokinetics
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Adenine / urine
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Administration, Oral
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Adult
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Antiretroviral Therapy, Highly Active
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Case-Control Studies
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Drug Interactions
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Female
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Genotype
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HIV Infections / drug therapy*
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HIV Infections / genetics
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HIV Infections / metabolism
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HIV Protease Inhibitors / administration & dosage
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HIV Protease Inhibitors / pharmacology*
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Humans
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Kidney / drug effects*
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Kidney / metabolism
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Lopinavir
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Male
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Membrane Transport Proteins / genetics
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Membrane Transport Proteins / metabolism
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Middle Aged
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Multidrug Resistance-Associated Protein 2
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Multidrug Resistance-Associated Proteins / genetics
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Multidrug Resistance-Associated Proteins / metabolism
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Organic Anion Transport Protein 1 / genetics
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Organic Anion Transport Protein 1 / metabolism
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Organophosphonates / administration & dosage
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Organophosphonates / pharmacokinetics*
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Organophosphonates / urine
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Pyrimidinones / administration & dosage
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Pyrimidinones / pharmacology*
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Reverse Transcriptase Inhibitors / administration & dosage
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Reverse Transcriptase Inhibitors / pharmacokinetics*
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Reverse Transcriptase Inhibitors / urine
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Ritonavir / administration & dosage
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Ritonavir / pharmacology*
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Tenofovir
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Treatment Outcome
Substances
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ABCC4 protein, human
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HIV Protease Inhibitors
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Membrane Transport Proteins
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Multidrug Resistance-Associated Protein 2
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Multidrug Resistance-Associated Proteins
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Organic Anion Transport Protein 1
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Organophosphonates
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Pyrimidinones
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Reverse Transcriptase Inhibitors
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Lopinavir
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Tenofovir
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Adenine
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Ritonavir