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Population Pharmacokinetic and Pharmacogenomic Analysis of Tacrolimus in Pediatric Living-donor Liver Transplant Recipients by FUKUDO, M; YANO, I; MASUDA, S; GOTO, M; UESUGI, M; KATSURA, T; OGURA, Y; OIKE, F; TAKADA, Y; EGAWA, H is a Medicine article available to read on EtoBox.

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## Objective: Our objective was to investigate the population pharmacokinetics of tacrolimus in pediatric living-donor liver transplant recipients and examine the effects of the multidrug resistance 1 (mdr1) gene and the cytochrome p450 (cyp) genes cyp3a4 and cyp3a5 on the oral clearance of tacrolimus. ## Methods: Data were collected retrospectively from 130 de novo pediatric liver transplant recipients treated with tacrolimus during the first 50 postoperative days. pharmacogenomic data including both the cyp3a5\*3 polymorphism and messenger ribonucleic acid (mrna) expression levels of mdr1, cyp3a4, and cyp3a5 in the native intestine and the graft liver at transplantation were obtained from 65 of the recipients. population pharmacokinetic analysis was performed with the nonlinear mixed-effects modeling program nonmem to estimate population mean parameters of apparent clearance (cl/f) and apparent volume of distribution (v/f). ## Results: Both cl/f and v/f were allometrically related to body weight, and cl/f decreased when the ast value was elevated. cl/f increased linearly in the immediate postoperative period but did not change with time after postoperative day 21. the intestinal

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Author

FUKUDO, M; YANO, I; MASUDA, S; GOTO, M; UESUGI, M; KATSURA, T; OGURA, Y; OIKE, F; TAKADA, Y; EGAWA, H

Publisher

Nature Publishing Group; Wiley (Blackwell Publishing); Wiley-Blackwell; Wiley; Springer Science and Business Media LLC; Research Square (ISSN 0009-9236)

Published

2006

Language

EN

Field

Medicine (Health Sciences)