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Clin Infect Dis. 2015 Aug 15;61(4):633-9. doi: 10.1093/cid/civ346. Epub 2015 Apr 28.

Plasma and Intracellular Pharmacokinetics of Tenofovir Disoproxil Fumarate 300 mg Every 48 Hours vs 150 mg Once Daily in HIV-Infected Adults With Moderate Renal Function Impairment.

Author information

1
Program for HIV Prevention and Treatment, Faculty of Associated Medical Sciences, Chiang Mai University, Thailand Harvard School of Public Health, Boston, Massachusetts Institut de Recherche pour le Développement UMI 174-Program for HIV Prevention and Treatment, Marseille, France.
2
HIV Netherlands Australia Thailand Research Collaboration, Thai Red Cross AIDS Research Centre Division of Allergy and Immunology, Faculty of Medicine, Chulalongkorn University, Bangkok.
3
Phayao Hospital.
4
Nakornping Hospital, Chiang Mai, Thailand.
5
Program for HIV Prevention and Treatment, Faculty of Associated Medical Sciences, Chiang Mai University, Thailand.
6
Antiviral Pharmacology Laboratory, College of Pharmacy, University of Nebraska Medical Center, Omaha.
7
Sanpatong Hospital, Chiang Mai.
8
Chonburi Hospital, Thailand.

Abstract

BACKGROUND:

The approved tenofovir disoproxil fumarate (TDF) dose of 300 mg every 48 hours for adults with moderate renal impairment is often confusing and inconvenient. Using a new TDF formulation, we compared the pharmacokinetics of the standard dose with a dose of 150 mg once daily in HIV-infected adults.

METHODS:

This was an open-label pharmacokinetic study. Virologically suppressed HIV-infected adults with a creatinine clearance 30 to <50 mL/minute receiving TDF 300 mg every 48 hours as part of a nonnucleoside reverse transcriptase inhibitor (NNRTI)- or lopinavir/ritonavir (LPV/r)-based regimen were enrolled. Intensive 48-hour blood sampling for pharmacokinetic assessment was performed at enrollment, after which the TDF dose was changed to 150 mg once daily. Two weeks later, 24-hour blood sampling was performed; subjects then returned to the standard dose. Tenofovir (TFV) pharmacokinetic parameters were calculated using a noncompartmental analysis.

RESULTS:

Forty adults (55% female) were enrolled: 20 receiving NNRTI-based and 20 receiving LPV/r-based treatment. Median age was 56 years (range, 44-65 years), weight 51 kg (range, 38-80 kg), and creatinine clearance 43.9 mL/minute (range, 30.9-49.7 mL/minute). The TFV geometric mean ratio of the area under the curve (AUC0-48 h) for every 24 hours vs every 48 hours was 1.09 (90% confidence interval [CI], .98-1.22) and 1.00 (90% CI, .92-1.09) for patients receiving NNRTI- and LPV/r-based treatment, respectively. Concomitant LPV/r use markedly increased TFV plasma concentrations, and AUC0-48 h was 67% higher with the standard dose, whereas no differences in intracellular TFV diphosphate concentrations were observed. All subjects remained virologically suppressed, and no drug-related adverse events were reported.

CONCLUSIONS:

TDF 150 mg every 24 hours provides comparable systemic exposure to the standard dose of 300 mg every 48 hours in patients with moderate renal impairment.

CLINICAL TRIALS REGISTRATION:

NCT01671982.

KEYWORDS:

HIV; kidney dysfunction; tenofovir

PMID:
25921689
PMCID:
PMC4607735
DOI:
10.1093/cid/civ346
[Indexed for MEDLINE]
Free PMC Article

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