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Population pharmacokinetics of abacavir and lamivudine in severely malnourished HIV-infected children in relation to treatment outcomes.

Br J Clin Pharmacol. 2019 May 29;:

Authors: Archary M, Mcllleron H, Bobat R, LaRussa P, Sibaya T, Wiesner L, Hennig S

Abstract
AIM: Describe the pharmacokinetics (PK) of the antiretroviral drugs abacavir and lamivudine in malnourished pediatric patients and relate to viral load outcomes after 12 and 48 weeks of treatment.
METHODS: Severely malnourished HIV-infected children were randomized to early (within 14 days) or delayed (after nutritional recovery) initiation of antiretroviral treatment (ART) using WHO weight-band dosages. Abacavir and lamivudine concentrations were measured as a secondary objective on day 1 and day 14 and patients were followed-up to week 48. Population pharmacokinetics of abacavir and lamivudine were described using NONMEM.
RESULTS: 623 abacavir and 627 lamivudine concentrations were collected from 75 paediatric patients aged 0.1-10.8 (median 1.4) years. Abacavir pharmacokinetics was described by a two-compartment model, patients randomised to early ART showed increased bioavilability of 31%. Apparent clearance (CL/F, L/h/7kg) of abacavir increased from day 1 to day 14 from 3.33 (95%CI:2.71 – 4.12) to 5.86 (95%CI 4.78 – 7.3). A one-compartment model described lamivudine pharmacokinetics, varibility on CL/F was explained by maturation with age, with age at half-matured CL/F being 4 months. For both drugs allometrically scaled total body weight was related to CL/F and apparent volume of distribution. Pharmacokinetic exposure did not correlate with virologic outcomes or death at 12 or 48 weeks.
CONCLUSIONS: Increases in Abacavir’s CL/F between day 1 to day 14, bioavailablity and PK varibility with early start of ART was found in this cohort of severly malnourished children, however these changes did not influence virological outcomes. The study supports the use of weight-band dosage tables.

PMID: 31141195 [PubMed – as supplied by publisher]

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