PMID- 34896748
OWN - NLM
STAT- MEDLINE
DCOM- 20220131
LR  - 20220131
IS  - 1880-0920 (Electronic)
IS  - 1347-4367 (Linking)
VI  - 42
DP  - 2022 Feb
TI  - Extrapolation of physiologically based pharmacokinetic model for tacrolimus from 
      renal to liver transplant patients.
PG  - 100423
LID - S1347-4367(21)00044-6 [pii]
LID - 10.1016/j.dmpk.2021.100423 [doi]
AB  - 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.
CI  - Copyright (c) 2021 The Japanese Society for the Study of Xenobiotics. Published by 
      Elsevier Ltd. All rights reserved.
FAU - Itohara, Kotaro
AU  - Itohara K
AD  - Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, 
      Sakyo-ku, Kyoto, 606-8507, Japan.
FAU - Yano, Ikuko
AU  - Yano I
AD  - Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, 
      Sakyo-ku, Kyoto, 606-8507, Japan; Department of Pharmacy, Kobe University 
      Hospital, Chuo-ku, Kobe, 650-0017, Japan. Electronic address: 
      iyano@med.kobe-u.ac.jp.
FAU - Nakagawa, Shunsaku
AU  - Nakagawa S
AD  - Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, 
      Sakyo-ku, Kyoto, 606-8507, Japan.
FAU - Yonezawa, Atsushi
AU  - Yonezawa A
AD  - Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, 
      Sakyo-ku, Kyoto, 606-8507, Japan; Graduate School of Pharmaceutical Sciences, 
      Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan.
FAU - Omura, Tomohiro
AU  - Omura T
AD  - Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, 
      Sakyo-ku, Kyoto, 606-8507, Japan; Department of Pharmacy, Kobe University 
      Hospital, Chuo-ku, Kobe, 650-0017, Japan.
FAU - Imai, Satoshi
AU  - Imai S
AD  - Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, 
      Sakyo-ku, Kyoto, 606-8507, Japan.
FAU - Nakagawa, Takayuki
AU  - Nakagawa T
AD  - Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, 
      Sakyo-ku, Kyoto, 606-8507, Japan.
FAU - Sawada, Atsuro
AU  - Sawada A
AD  - Department of Urology, Graduate School of Medicine, Kyoto University, Sakyo-ku, 
      Kyoto, 606-8501, Japan.
FAU - Kobayashi, Takashi
AU  - Kobayashi T
AD  - Department of Urology, Graduate School of Medicine, Kyoto University, Sakyo-ku, 
      Kyoto, 606-8501, Japan.
FAU - Tochio, Akira
AU  - Tochio A
AD  - Department of Nephrology, Graduate School of Medicine, Kyoto University, 
      Sakyo-ku, Kyoto, 606-8501, Japan.
FAU - Sakai, Kaoru
AU  - Sakai K
AD  - Department of Nephrology, Graduate School of Medicine, Kyoto University, 
      Sakyo-ku, Kyoto, 606-8501, Japan.
FAU - Taura, Kojiro
AU  - Taura K
AD  - Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of 
      Surgery, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, 
      606-8501, Japan.
FAU - Ogawa, Osamu
AU  - Ogawa O
AD  - Department of Urology, Graduate School of Medicine, Kyoto University, Sakyo-ku, 
      Kyoto, 606-8501, Japan.
FAU - Matsubara, Kazuo
AU  - Matsubara K
AD  - Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, 
      Sakyo-ku, Kyoto, 606-8507, Japan.
LA  - eng
PT  - Journal Article
DEP - 20211001
PL  - England
TA  - Drug Metab Pharmacokinet
JT  - Drug metabolism and pharmacokinetics
JID - 101164773
RN  - 0 (Immunosuppressive Agents)
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
MH  - Humans
MH  - Immunosuppressive Agents
MH  - Kidney
MH  - *Kidney Transplantation
MH  - *Liver Transplantation
MH  - Models, Biological
MH  - Tacrolimus
OTO - NOTNLM
OT  - Liver transplantation
OT  - PBPK
OT  - Renal transplantation
OT  - Simcyp
OT  - Tacrolimus
COIS- Declaration of competing interest None of the authors have any competing 
      interests to declare.
EDAT- 2021/12/14 06:00
MHDA- 2022/02/01 06:00
CRDT- 2021/12/13 12:54
PHST- 2021/05/25 00:00 [received]
PHST- 2021/08/18 00:00 [revised]
PHST- 2021/09/27 00:00 [accepted]
PHST- 2021/12/14 06:00 [pubmed]
PHST- 2022/02/01 06:00 [medline]
PHST- 2021/12/13 12:54 [entrez]
AID - S1347-4367(21)00044-6 [pii]
AID - 10.1016/j.dmpk.2021.100423 [doi]
PST - ppublish
SO  - Drug Metab Pharmacokinet. 2022 Feb;42:100423. doi: 10.1016/j.dmpk.2021.100423. 
      Epub 2021 Oct 1.