Extrapolation of physiologically based pharmacokinetic model for tacrolimus from renal to liver transplant patients.
Drug Metab Pharmacokinet
; 42: 100423, 2022 Feb.
Article
em En
| MEDLINE
| ID: mdl-34896748
ABSTRACT
Physiologically based pharmacokinetic (PBPK) modeling is useful for evaluating differences in drug exposure among special populations, but it has not yet been employed to evaluate the absorption process of tacrolimus. In this study, we developed a minimal PBPK model with a compartmental absorption and transit model for renal transplant patients using available data in the literature and clinical data from our hospital. The effective permeability value of tacrolimus absorption and parameters for the single adjusting compartment were optimized via sensitivity analyses, generating a PBPK model of tacrolimus for renal transplant patients with good predictability. Next, we extrapolated the pharmacokinetics of tacrolimus for liver transplant patients by changing the population demographic parameters of the model. When the physiological parameters of a population with normal liver function were changed to those of a population with impaired hepatic function (Child-Pugh class A) in the constructed renal transplant PBPK model, the predicted tacrolimus concentrations were consistent with the observed concentrations in liver transplant patients. In conclusion, the constructed tacrolimus PBPK model for renal transplant patients could predict the pharmacokinetics in liver transplant patients by slightly reducing the hepatic function, even at three weeks post-transplantation.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transplante de Rim
/
Transplante de Fígado
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Drug Metab Pharmacokinet
Assunto da revista:
FARMACOLOGIA
/
METABOLISMO
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Japão