Lopinavir exposure is insufficient in children given double doses of lopinavir/ritonavir during rifampicin-based treatment for tuberculosis

Date
2011
Authors
McIlleron H.
Ren Y.
Nuttall J.
Fairlie L.
Rabie H.
Cotton M.
Eley B.
Meyers T.
Smith P.J.
Merry C.
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Background: Coadministration of rifampicin dramatically reduces the concentrations of protease inhibitors. A pharmacokinetic study in healthy adults showed that doubling the dose of coformulated lopinavir/ritonavir was able to overcome the inducing effect of rifampicin. We evaluated this strategy in children treated with rifampicin-based antituberculosis therapy attending antiretroviral clinics in South Africa. Methods: Plasma concentrations of lopinavir were measured in children (aged 0.64-2.43 years) established on antituberculosis treatment who commenced antiretroviral therapy comprising double the usual recommended dose of lopinavir/ritonavir oral solution (460/115 mg/m2 twice daily) plus two nucleoside reverse transcriptase inhibitors. Control children (0.57-4.23 years old) without tuberculosis received standard doses of lopinavir/ritonavir (230/57.5 mg/m2 twice daily). Results: Pre-dose lopinavir concentrations were reduced by >80% in children with tuberculosis (median 0.7 mg/l, IQR 0.1-2.0) compared with controls (4.2 mg/l, IQR 3.4-8.1; P<0.001) and were below the minimum recommended concentration of 1 mg/l in 12 of 20 (60%) children with tuberculosis versus 2 of 24 (8%) controls (P<0.001). Conclusions: Double doses of coformulated lopinavir/ritonavir results in inadequate lopinavir concentrations in young children treated concurrently with rifampicin. Suitable regimens are urgently needed for treating young children with HIV-associated tuberculosis. ©2011 International Medical Press.
Description
Keywords
lopinavir, lopinavir plus ritonavir, rifampicin, RNA directed DNA polymerase inhibitor, area under the curve, article, child, clinical article, controlled study, drug blood level, drug dose increase, drug exposure, drug inhibition, drug monitoring, female, human, Human immunodeficiency virus infection, infant, male, maximum plasma concentration, plasma concentration-time curve, preschool child, priority journal, recommended drug dose, South Africa, tuberculosis, virus load, Anti-HIV Agents, Antitubercular Agents, Child, Preschool, Drug Interactions, Drug Therapy, Combination, Female, HIV, HIV Infections, Humans, Infant, Male, Pyrimidinones, Rifampin, Ritonavir, South Africa, Treatment Outcome, Tuberculosis
Citation
Antiviral Therapy
16
3
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