Population pharmacokinetics and pharmacodynamics of nelfinavir and its active metabolite M8 in HIV-1-infected children.
Pediatr Infect Dis J
; 25(6): 538-43, 2006 Jun.
Article
em En
| MEDLINE
| ID: mdl-16732153
ABSTRACT
BACKGROUND:
The objectives of this study are to develop and validate a population pharmacokinetic model that adequately describes the pharmacokinetics of nelfinavir and its active metabolite M8 in HIV-1-infected children; to define factors involved in the pharmacokinetic variability, which could aid in defining dosing strategies; and to correlate the pharmacokinetics to the treatment response.METHODS:
Protease inhibitor-naive, HIV-1-infected children were included. A population pharmacokinetic model of nelfinavir and M8 was developed using NONMEM. Bayesian analysis was used to estimate pharmacokinetic values. A pharmacokinetic-pharmacodynamic analysis was performed to study relationships between these values and the virologic response to therapy.RESULTS:
From 38 children, 724 nelfinavir and 636 M8 plasma concentrations were available. The pharmacokinetics of both compounds were described simultaneously with a one-compartment model with first-order elimination. Clearance (CL/F) and volume of distribution (V/F) were 32.6 L/h (interindividual variability [IIV] 31.6%) and 281 L/h (IIV 29.7%) for nelfinavir and 86.2 L/h (IIV 43.1%) and 42.3 L/h for M8. No factors could be defined that affected the pharmacokinetics of nelfinavir or M8. The overall virologic response was 78% (HIV-1 RNA <500 copies/mL, on-treatment analysis). No differences in exposure to nelfinavir and M8 were observed between responders and nonresponders. The only factor distinguishing the two groups was a higher baseline HIV-1 RNA concentration in nonresponders.CONCLUSION:
A model was developed and validated that adequately described the population pharmacokinetics of nelfinavir and M8 in a childhood population. No factors affecting dosing strategies were identified, and no correlation could be demonstrated between the exposure to nelfinavir and M8 and the virologic treatment response.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tetra-Hidronaftalenos
/
Infecções por HIV
/
Inibidores da Protease de HIV
/
Nelfinavir
Tipo de estudo:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adolescent
/
Child
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
País/Região como assunto:
Europa
Idioma:
En
Revista:
Pediatr Infect Dis J
Assunto da revista:
DOENCAS TRANSMISSIVEIS
/
PEDIATRIA
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Holanda