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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Pharmacokinetics of lopinavir in HIV-infected adults receiving rifampin with adjusted doses of lopinavir-ritonavir tablets
Antimicrobial Agents and Chemotherapy, Volume 55, No. 7, Year 2011
Notification
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Description
Rifampin coadministration dramatically reduces plasma lopinavir (LPV) concentrations. In healthy volunteers, doubling the dose of a lopinavir-ritonavir (LPV/r) capsule formulation overcame this interaction, but a subsequent study of double doses of the tablet formulation was stopped early owing to hepatotoxicity. However, healthy-volunteer study findings may not apply to HIV-infected adults. We evaluated the steady-state pharmacokinetics of LPV in HIV-infected adults virologically suppressed on an LPV/r regimen who were given rifampin, and the dose of the LPV/r tablet formulation was gradually increased. The steady-state pharmacokinetics of LPV/r were evaluated at baseline, a week after commencing rifampin, a week after the LPV/r dose was increased 1.5 times, and a week after the LPV/r dose was doubled. Twenty-one participants were enrolled. The median [interquartile range (IQR)] predose LPV concentrations (C0) were 8.1 (6.2 to 9.8) mg/liter at baseline, 1.7 (0.3 to 3.0) mg/liter after 7 days of rifampin, 5.9 (2.1 to 9.9) mg/liter with 1.5 times the dose of LPV/r, and 10.8 (7.0 to 13.1) mg/liter with double-dose LPV/r. There were no significant differences in the LPV area under the plasma concentration-time curve from 0 to 12 h (AUC0-12), C0, C12, maximum concentration of drug in serum (Cmax), or half-life (t1/2) between the baseline and double-dose LPV/r time points. Treatment was generally well tolerated, with two participants developing asymptomatic grade 3/4 transaminitis. Doubling the dose of the tablet formulation of LPV/r overcomes induction by rifampin. Less hepatotoxicity occurred in our cohort of HIV-infected participants than was reported in healthy-volunteer studies. Copyright © 2011, American Society for Microbiology. All Rights Reserved.
Authors & Co-Authors
Decloedt, Eric H.
South Africa, Cape Town
Faculty of Health Sciences
McIlleron, Helen Margaret
South Africa, Cape Town
Faculty of Health Sciences
Smith, Peter John
South Africa, Cape Town
Faculty of Health Sciences
Merry, Concepta
Ireland, Dublin
St James's Hospital
Orrell, Catherine J.
South Africa, Cape Town
University of Cape Town
Maartens, Gary Tuberculosis
South Africa, Cape Town
Faculty of Health Sciences
Statistics
Citations: 53
Authors: 6
Affiliations: 3
Identifiers
Doi:
10.1128/AAC.01598-10
ISSN:
00664804
e-ISSN:
10986596
Research Areas
Infectious Diseases
Study Design
Cohort Study