Abacavir Drug Exposures in African Children Under 14 kg Using Pediatric Solid Fixed Dose Combinations According to World Health Organization Weight Bands.
J Pediatric Infect Dis Soc
; 12(11): 574-580, 2023 Nov 30.
Article
em En
| MEDLINE
| ID: mdl-37798141
ABSTRACT
BACKGROUND:
The pharmacokinetics of abacavir (ABC) in African children living with HIV (CLHIV) weighing <14 kg and receiving pediatric fixed dose combinations (FDC) according to WHO weight bands dosing are limited. An ABC population pharmacokinetic model was developed to evaluate ABC exposure across different World Health Organization (WHO) weight bands.METHODS:
Children enrolled in the LIVING study in Kenya and Uganda receiving ABC/lamivudine (3TC) dispersible tablets (60/30 mg) according to WHO weight bands. A population approach was used to determine the pharmacokinetic parameters. Monte Carlo simulations were conducted using an in silico population with demographic characteristics associated with African CLHIV. ABC exposures (AUC0-24) of 6.4-50.4 mg h/L were used as targets.RESULTS:
Plasma samples were obtained from 387 children. A 1-compartment model with allometric scaling of clearance (CL/F) and volume of distribution (V/F) according to body weight best characterized the pharmacokinetic data of ABC. The maturation of ABC CL/F was characterized using a sigmoidal Emax model dependent on postnatal age (50% of adult CL/F reached by 0.48 years of age). Exposures to ABC were within the target range for children weighing 6.0-24.9 kg, but children weighing 3-5.9 kg were predicted to be overexposed.CONCLUSIONS:
Lowering the ABC dosage to 30 mg twice daily or 60 mg once daily for children weighing 3-5.9 kg increased the proportion of children within the target and provided comparable exposures. Further clinical study is required to investigate clinical implications and safety of the proposed alternative ABC doses.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
11_ODS3_cobertura_universal
/
2_ODS3
Base de dados:
MEDLINE
Assunto principal:
Infecções por HIV
/
Fármacos Anti-HIV
Tipo de estudo:
Prognostic_studies
Aspecto:
Patient_preference
Limite:
Adult
/
Child
/
Humans
/
Infant
País/Região como assunto:
Africa
Idioma:
En
Revista:
J Pediatric Infect Dis Soc
Ano de publicação:
2023
Tipo de documento:
Article