Population Pharmacokinetics of Methylphenidate in Healthy Adults Emphasizing Novel and Known Effects of Several Carboxylesterase 1 (CES1) Variants.
Clin Transl Sci
; 9(6): 337-345, 2016 12.
Article
em En
| MEDLINE
| ID: mdl-27754602
ABSTRACT
The aim of this study was to identify demographic and genetic factors that significantly affect methylphenidate (MPH) pharmacokinetics (PK), and may help explain interindividual variability and further increase the safety of MPH. d-MPH plasma concentrations, demographic covariates, and carboxylesterase 1 (CES1) genotypes were gathered from 122 healthy adults and analyzed using nonlinear mixed effects modeling. The structural model that best described the data was a two-compartment disposition model with absorption transit compartments. Novel effects of rs115629050 and CES1 diplotypes, as well as previously reported effects of rs71647871 and body weight, were included in the final model. Assessment of the independent and combined effect of CES1 covariates identified several specific risk factors that may result in severely increased d-MPH plasma exposure.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Variação Genética
/
Hidrolases de Éster Carboxílico
/
Metilfenidato
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article