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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Effect of rifampicin on lopinavir pharmacokinetics in HIV-infected children with tuberculosis
Journal of Acquired Immune Deficiency Syndromes, Volume 47, No. 5, Year 2008
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Description
OBJECTIVE: Rifampicin dramatically reduces plasma lopinavir concentrations (coformulated with ritonavir in a 4:1 ratio). A study in healthy adult volunteers showed that this reduction could be ameliorated if additional ritonavir is given. We evaluated the effect of additional ritonavir on plasma lopinavir concentrations in HIV-infected children receiving rifampicin-based treatment for tuberculosis. METHODS: We measured plasma lopinavir concentrations in 2 parallel groups receiving combination antiretroviral therapy that included lopinavir-ritonavir, with and without rifampicin-based antitubercular treatment. Additional ritonavir was given (lopinavir/ritonavir ratio of 1:1) during antitubercular treatment. Lopinavir concentrations were determined using liquid chromatography-tandem mass spectrometry. RESULTS: There were 15 children (aged 7 months to 3.9 years) in each group. Lopinavir pharmacokinetic measures (median [interquartile range]) for children with and without rifampicin, respectively, were maximum concentration (Cmax) of 10.5 [7.1 to 14.3] versus 14.2 [11.9 to 23.5] mg/L (P = 0.018), area under the curve from 0 to 12 hours (AUC0-12) of 80.9 [50.9 to 121.7] versus 117.8 [80.4 to 176.1] mg/h/L (P = 0.036), and trough concentration (Cmin) of 3.94 [2.26 to 7.66] versus 4.64 [2.32 to 10.40] mg/L (P = 0.468). Thirteen of 15 children receiving antitubercular treatment (87%) had a lopinavir Cmin greater than the recommended minimum therapeutic concentration (1 mg/L). CONCLUSIONS: The effect of rifampicin-based antitubercular treatment on lopinavir concentrations was attenuated by adding ritonavir to rifampicin. Although the median Cmax and AUC0-12 were lowered by 26% and 31%. respectively, the Cmin was greater than the minimum recommended concentration in most children. © 2008 Lippincott Williams & Wilkins, Inc.
Authors & Co-Authors
Ren, Yuan
South Africa, Cape Town
University of Cape Town
Nuttall, James J.C.
South Africa, Cape Town
University of Cape Town
Egbers, Claire
South Africa, Johannesburg
Chris Hani Baragwanath Hospital
South Africa, Johannesburg
University of the Witwatersrand
Eley, Brian S.
South Africa, Cape Town
University of Cape Town
Meyers, Tammy M.M.
South Africa, Johannesburg
Chris Hani Baragwanath Hospital
South Africa, Johannesburg
University of the Witwatersrand
Smith, Peter J.D.
South Africa, Cape Town
University of Cape Town
Maartens, Gary Tuberculosis
South Africa, Cape Town
University of Cape Town
McIlleron, Helen Margaret
South Africa, Cape Town
University of Cape Town
South Africa, Observatory
Groote Schuur Hospital
Statistics
Citations: 109
Authors: 8
Affiliations: 4
Identifiers
Doi:
10.1097/QAI.0b013e3181642257
ISSN:
15254135
Research Areas
Infectious Diseases
Maternal And Child Health