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Pharmacokinetics and Drug-Drug Interactions of Abacavir and Lamuvudine Co-administered With Antituberculosis Drugs in HIV-Positive Children Treated for Multidrug-Resistant Tuberculosis
- Source :
- Frontiers in Pharmacology, Vol 12 (2021), Frontiers in Pharmacology
- Publication Year :
- 2021
- Publisher :
- Frontiers Media S.A., 2021.
-
Abstract
- Given 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.
- Subjects :
- Population
Terizidone
RM1-950
Pharmacology
Pharmacokinetics
Abacavir
immune system diseases
medicine
Pharmacology (medical)
education
Ethambutol
education.field_of_study
business.industry
paediatrics (drugs and medicines)
Lamivudine
virus diseases
HIV
Pyrazinamide
Brief Research Report
pharmacometric modeling
tuberculosis
Ethionamide
drug drug interactions
Therapeutics. Pharmacology
business
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 16639812
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Frontiers in Pharmacology
- Accession number :
- edsair.doi.dedup.....b2ad8f39dd87e57431a807a4dae93caa