Back to Search
Start Over
Extrapolation of physiologically based pharmacokinetic model for tacrolimus from renal to liver transplant patients.
- Source :
-
Drug metabolism and pharmacokinetics [Drug Metab Pharmacokinet] 2022 Feb; Vol. 42, pp. 100423. Date of Electronic Publication: 2021 Oct 01. - Publication Year :
- 2022
-
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.<br />Competing Interests: Declaration of competing interest None of the authors have any competing interests to declare.<br /> (Copyright © 2021 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.)
Details
- Language :
- English
- ISSN :
- 1880-0920
- Volume :
- 42
- Database :
- MEDLINE
- Journal :
- Drug metabolism and pharmacokinetics
- Publication Type :
- Academic Journal
- Accession number :
- 34896748
- Full Text :
- https://doi.org/10.1016/j.dmpk.2021.100423