Model based development of tacrolimus dosing algorithm considering CYP3A5 genotypes and mycophenolate mofetil drug interaction in stable kidney transplant recipients

Abstract This study quantifies the interaction between tacrolimus (TAC) and mycophenolate mofetil (MMF) in kidney transplant recipients. Concentrations of TAC, mycophenolic acid (MPA), and metabolites were analyzed and relevant genotypes were determined from 32 patients. A population model was devel...

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Autores principales:	Jae Hyun Kim, Nayoung Han, Myeong Gyu Kim, Young Won Kim, Hayoung Jang, Hwi-Yeol Yun, Mi-Yeon Yu, In-Wha Kim, Yon Su Kim, Jung Mi Oh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/145ab1dcf707415c97b7cd739eaf13fa
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spelling	oai:doaj.org-article:145ab1dcf707415c97b7cd739eaf13fa2021-12-02T16:08:27ZModel based development of tacrolimus dosing algorithm considering CYP3A5 genotypes and mycophenolate mofetil drug interaction in stable kidney transplant recipients10.1038/s41598-019-47876-02045-2322https://doaj.org/article/145ab1dcf707415c97b7cd739eaf13fa2019-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-47876-0https://doaj.org/toc/2045-2322Abstract This study quantifies the interaction between tacrolimus (TAC) and mycophenolate mofetil (MMF) in kidney transplant recipients. Concentrations of TAC, mycophenolic acid (MPA), and metabolites were analyzed and relevant genotypes were determined from 32 patients. A population model was developed to estimate the effect of interaction. Concentrations of TAC were simulated in clinical scenarios and dose-adjusted trough concentrations per dose (C/D) were compared. Effect of interaction was described as the inverse exponential relationship. Major determinants of trough levels of TAC were CYP3A5 genotype and interaction with MPA. The absolute difference in C/D of TAC according to co-administered MMF was higher in CYP3A5 non-expressers (0.55 ng/mL) than in CYP3A5 expressers (0.35 ng/mL). The effect of MMF in determining the TAC exposure is more pronounced in CYP3A5 non-expressers. Based on population pharmacokinetic model, we suggest the TAC dosing algorithm considering the effects of CYP3A5 and MMF drug interaction in stable kidney transplant recipients.Jae Hyun KimNayoung HanMyeong Gyu KimYoung Won KimHayoung JangHwi-Yeol YunMi-Yeon YuIn-Wha KimYon Su KimJung Mi OhNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-9 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jae Hyun Kim Nayoung Han Myeong Gyu Kim Young Won Kim Hayoung Jang Hwi-Yeol Yun Mi-Yeon Yu In-Wha Kim Yon Su Kim Jung Mi Oh Model based development of tacrolimus dosing algorithm considering CYP3A5 genotypes and mycophenolate mofetil drug interaction in stable kidney transplant recipients
description	Abstract This study quantifies the interaction between tacrolimus (TAC) and mycophenolate mofetil (MMF) in kidney transplant recipients. Concentrations of TAC, mycophenolic acid (MPA), and metabolites were analyzed and relevant genotypes were determined from 32 patients. A population model was developed to estimate the effect of interaction. Concentrations of TAC were simulated in clinical scenarios and dose-adjusted trough concentrations per dose (C/D) were compared. Effect of interaction was described as the inverse exponential relationship. Major determinants of trough levels of TAC were CYP3A5 genotype and interaction with MPA. The absolute difference in C/D of TAC according to co-administered MMF was higher in CYP3A5 non-expressers (0.55 ng/mL) than in CYP3A5 expressers (0.35 ng/mL). The effect of MMF in determining the TAC exposure is more pronounced in CYP3A5 non-expressers. Based on population pharmacokinetic model, we suggest the TAC dosing algorithm considering the effects of CYP3A5 and MMF drug interaction in stable kidney transplant recipients.
format	article
author	Jae Hyun Kim Nayoung Han Myeong Gyu Kim Young Won Kim Hayoung Jang Hwi-Yeol Yun Mi-Yeon Yu In-Wha Kim Yon Su Kim Jung Mi Oh
author_facet	Jae Hyun Kim Nayoung Han Myeong Gyu Kim Young Won Kim Hayoung Jang Hwi-Yeol Yun Mi-Yeon Yu In-Wha Kim Yon Su Kim Jung Mi Oh
author_sort	Jae Hyun Kim
title	Model based development of tacrolimus dosing algorithm considering CYP3A5 genotypes and mycophenolate mofetil drug interaction in stable kidney transplant recipients
title_short	Model based development of tacrolimus dosing algorithm considering CYP3A5 genotypes and mycophenolate mofetil drug interaction in stable kidney transplant recipients
title_full	Model based development of tacrolimus dosing algorithm considering CYP3A5 genotypes and mycophenolate mofetil drug interaction in stable kidney transplant recipients
title_fullStr	Model based development of tacrolimus dosing algorithm considering CYP3A5 genotypes and mycophenolate mofetil drug interaction in stable kidney transplant recipients
title_full_unstemmed	Model based development of tacrolimus dosing algorithm considering CYP3A5 genotypes and mycophenolate mofetil drug interaction in stable kidney transplant recipients
title_sort	model based development of tacrolimus dosing algorithm considering cyp3a5 genotypes and mycophenolate mofetil drug interaction in stable kidney transplant recipients
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/145ab1dcf707415c97b7cd739eaf13fa
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Model based development of tacrolimus dosing algorithm considering CYP3A5 genotypes and mycophenolate mofetil drug interaction in stable kidney transplant recipients

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