Extrapolation of physiologically based pharmacokinetic model for tacrolimus from renal to liver transplant patients |
| |
| Affiliation: | 1. Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Sakyo-ku, Kyoto, 606-8507, Japan;2. Department of Pharmacy, Kobe University Hospital, Chuo-ku, Kobe, 650-0017, Japan;3. Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan;4. Department of Urology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan;5. Department of Nephrology, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan;6. Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan;1. Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aramaki-Aoba, Aoba-ku, Sendai, 980-8578, Japan;2. Division of Risk Assessment, National Institute of Health Sciences, Tonomachi 3-25-26, Kawasaki-ku, Kanagawa, 210-9501, Japan;3. Regulatory Science, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1, Tanabe-dori, Mizuho-ku, Nagoya, 467-8603, Japan;1. Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Japan;2. Pharmacokinetics and Bioanalysis Center, Shin Nippon Biomedical Laboratories, Ltd., Kainan, Japan;3. Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Japan;1. Discovery Technology Laboratories, Sohyaku Innovative Research Division, Mitsubishi Tanabe Pharma Corporation, Kanagawa, Japan;2. Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Tokyo, Japan;1. Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aramaki-Aoba, Aoba-ku, Sendai, 980-8578, Japan;2. Division of Risk Assessment, National Institute of Health Sciences, Tonomachi 3-25-26, Kawasaki-ku, Kanagawa, 210-9501, Japan;3. Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Tokyo, 194-8543, Japan;4. Laboratory of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan;1. Central Institute for Experimental Animals, Kawasaki, 210-0821, Japan;2. Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Tokyo, 194-8543, Japan;3. Institut de Chimie Organique et Analytique, University of Orléans, 45067, Orléans Cedex 2, France;1. Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Thailand;2. Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Thailand;3. Department of Pediatrics, Khon Kaen Hospital, Khon Kaen, Thailand;4. Department of Pediatrics, Udon Thani Hospital, Udon Thani, Thailand;5. Laboratory for Pharmacogenomics, RIKEN Center for Integrative Medical Sciences, Yokohama City, Kanagawa, Japan;6. Department of Pediatrics, Faculty of Medicine, Shimane University, Izumo, Japan |
| |
| 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. |
| |
| Keywords: | PBPK Tacrolimus Renal transplantation Liver transplantation Simcyp |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
