Pharmacokinetics and drug-drug interactions of abacavir and lamuvudine co-administered with antituberculosis drugs in HIV-positive children treated for multidrug-resistant tuberculosis

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dc.contributor.authorVan der Laan, Louvina E.en_ZA
dc.contributor.authorGarcia-Prats, Anthony J.en_Za
dc.contributor.authorSchaaf, H. Simonen_ZA
dc.contributor.authorWinckler, Jana L.en_ZA
dc.contributor.authorDraper, Heatheren_ZA
dc.contributor.authorNorman, Jenniferen_ZA
dc.contributor.authorWiesner, Lubbeen_ZA
dc.contributor.authorMcIlleron, Helenen_ZA
dc.contributor.authorDenti, Paoloen_ZA
dc.contributor.authorHesseling, Anneke C.en_ZA
dc.date.accessioned2023-04-26T07:22:46Zen_ZA
dc.date.available2023-04-26T07:22:46Zen_ZA
dc.date.issued2021-10-08en_ZA
dc.descriptionCITATION: van der Laan LE, Garcia-Prats AJ, Schaaf HS, Winckler JL, Draper H, Norman J, Wiesner L, McIlleron H, Denti P and Hesseling AC (2021) Pharmacokinetics and Drug-Drug Interactions of Abacavir and Lamuvudine Co-administered With Antituberculosis Drugs in HIV-Positive Children Treated for Multidrug-Resistant Tuberculosis. Front. Pharmacol. 12:722204. doi.10.3389/fphar.2021.722204en_ZA
dc.descriptionThe original publication is available at: frontiersin.orgen_ZA
dc.description.abstractGiven the high prevalence of multidrug-resistant (MDR)-TB in high HIV burden settings, it is important to identify potential drug-drug interactions between MDR-TB treatment and widely used nucleoside reverse transcriptase inhibitors (NRTIs) in HIV-positive children. Population pharmacokinetic models were developed for lamivudine (n = 54) and abacavir (n = 50) in 54 HIV-positive children established on NRTIs; 27 with MDR-TB (combinations of high-dose isoniazid, pyrazinamide, ethambutol, ethionamide, terizidone, fluoroquinolones, and amikacin), and 27 controls without TB. Two-compartment models with first-order elimination and transit compartment absorption described both lamivudine and abacavir pharmacokinetics, respectively. Allometric scaling with body weight adjusted for the effect of body size. Clearance was predicted to reach half its mature value ∼2 (lamivudine) and ∼3 (abacavir) months after birth, with completion of maturation for both drugs at ∼2 years. No significant difference was found in key pharmacokinetic parameters of lamivudine and abacavir when co-administered with routine drugs used for MDR-TB in HIV-positive children.en_ZA
dc.description.versionPublisher’s versionen_ZA
dc.format.extent9 pagesen_ZA
dc.identifier.citationvan der Laan LE, Garcia-Prats AJ, Schaaf HS, Winckler JL, Draper H, Norman J, Wiesner L, McIlleron H, Denti P and Hesseling AC (2021) Pharmacokinetics and Drug-Drug Interactions of Abacavir and Lamuvudine Co-administered With Antituberculosis Drugs in HIV-Positive Children Treated for Multidrug-Resistant Tuberculosis. Front. Pharmacol. 12:722204. doi.10.3389/fphar.2021.722204en_ZA
dc.identifier.issn1663-9812 (online)en_ZA
dc.identifier.otherdoi.10.3389/fphar.2021.722204en_ZA
dc.identifier.urihttp://hdl.handle.net/10019.1/126834en_ZA
dc.language.isoen_ZAen_ZA
dc.publisherFrontiers Media S.Aen_ZA
dc.rights.holderAuthors retain copyrighten_ZA
dc.subjectMultidrug-resistant tuberculosisen_ZA
dc.subjectHIV-positive childrenen_ZA
dc.subjectAntitubercular agentsen_ZA
dc.subjectPharmacokineticsen_ZA
dc.subjectPediatricsen_ZA
dc.titlePharmacokinetics and drug-drug interactions of abacavir and lamuvudine co-administered with antituberculosis drugs in HIV-positive children treated for multidrug-resistant tuberculosisen_ZA
dc.typeArticleen_ZA
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