Abstract | AIMS: METHODS: RESULTS: The bioavailability of lopinavir was reduced by 25% in adults whereas children on antituberculosis treatment experienced a 59% reduction, an effect that was moderated by the dose of ritonavir. Conversely, rifampicin increased oral clearance of both lopinavir and ritonavir to a lesser extent in children than in adults. Rifampicin therapy in administered doses increased CL of lopinavir by 58% in adults and 48% in children, and CL of ritonavir by 34% and 22% for adults and children, respectively. In children, the absorption half-life of lopinavir and the mean transit time of ritonavir were lengthened, compared with those in adults. CONCLUSIONS: The model characterized important differences between adults and children in the effect of rifampicin on the pharmacokinetics of lopinavir and ritonavir. As adult studies cannot reliably predict their magnitude in children, drug-drug interactions should be evaluated in paediatric patient populations.
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Authors | Chao Zhang, Paolo Denti, Eric H Decloedt, Yuan Ren, Mats O Karlsson, Helen McIlleron |
Journal | British journal of clinical pharmacology
(Br J Clin Pharmacol)
Vol. 76
Issue 5
Pg. 741-51
(Nov 2013)
ISSN: 1365-2125 [Electronic] England |
PMID | 23432610
(Publication Type: Controlled Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Copyright | © 2013 The Authors. British Journal of Clinical Pharmacology © 2013 The British Pharmacological Society. |
Chemical References |
- Anti-HIV Agents
- Antitubercular Agents
- Lopinavir
- Ritonavir
- Rifampin
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Topics |
- Adult
- Age Factors
- Anti-HIV Agents
(administration & dosage, pharmacokinetics, therapeutic use)
- Antitubercular Agents
(administration & dosage, pharmacokinetics, therapeutic use)
- Biological Availability
- Child, Preschool
- Cohort Studies
- Drug Interactions
- Female
- HIV Infections
(drug therapy)
- Half-Life
- Humans
- Infant
- Lopinavir
(administration & dosage, pharmacokinetics, therapeutic use)
- Male
- Middle Aged
- Models, Biological
- Nonlinear Dynamics
- Rifampin
(administration & dosage, pharmacokinetics, therapeutic use)
- Ritonavir
(administration & dosage, pharmacokinetics, therapeutic use)
- Tuberculosis
(drug therapy)
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