Population pharmacokinetics of abacavir and lamivudine in severely malnourished human immunodeficiency virus-infected children in relation to treatment outcomes.
Br J Clin Pharmacol
; 85(9): 2066-2075, 2019 09.
Article
en En
| MEDLINE
| ID: mdl-31141195
ABSTRACT
AIMS:
Describe the pharmacokinetics (PK) of the antiretroviral drugs abacavir and lamivudine in malnourished paediatric patients and relate to viral load outcomes after 12 and 48 weeks of treatment.METHODS:
Severely malnourished human immunodeficiency virus-infected children were randomized to early (within 14 days) or delayed (after nutritional recovery) initiation of antiretroviral treatment (ART) using World Health Organization 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 PK of abacavir and lamivudine were described using NONMEM.RESULTS:
In total, 623 abacavir and 627 lamivudine concentrations were collected from 75 paediatric patients aged 0.1-10.8 (median 1.4) years. Abacavir PK was described by a 2-compartment model, patients randomized to early ART showed increased bioavailability of 31%. Apparent clearance (CL/F, L/h/7 kg) of abacavir increased from day 1 to day 14 from 3.33 (95% confidence interval 2.71-4.12) to 5.86 (95% confidence interval 4.78-7.3). A 1-compartment model described lamivudine PK, variability 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. PK exposure did not correlate with virological outcomes or death at 12 or 48 weeks.CONCLUSION:
Increases in Abacavir's CL/F between day 1 to day 14, bioavailability and PK variability with early start of ART was found in this cohort of severely malnourished children; however, these changes did not influence virological outcomes. The study supports the use of weight-band dosage tables.Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Trastornos de la Nutrición del Niño
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Didesoxinucleósidos
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Infecciones por VIH
/
Lamivudine
/
Fármacos Anti-VIH
Tipo de estudio:
Clinical_trials
/
Diagnostic_studies
/
Etiology_studies
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Observational_studies
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Prognostic_studies
/
Risk_factors_studies
País/Región como asunto:
Africa
Idioma:
En
Revista:
Br J Clin Pharmacol
Año:
2019
Tipo del documento:
Article
País de afiliación:
Sudáfrica