Mechanisms of Lower Maintenance Dose of Tacrolimus in Obese Patients
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- SAWAMOTO Kazuki
- Department of Hospital Pharmacy, University Hospital, Kanazawa University Department of Clinical Pharmacy, Graduate School of Natural Science and Technology, Kanazawa University
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- HUONG Tran T.
- Department of Medical Informatics, Graduate School of Medical Sciences, Kanazawa University
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- SUGIMOTO Natsumi
- Department of Hospital Pharmacy, School of Pharmacy, Kanazawa University
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- MIZUTANI Yuka
- Department of Hospital Pharmacy, School of Pharmacy, Kanazawa University
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- SAI Yoshimichi
- Department of Hospital Pharmacy, University Hospital, Kanazawa University Department of Clinical Pharmacy, Graduate School of Natural Science and Technology, Kanazawa University Department of Medical Informatics, Graduate School of Medical Sciences, Kanazawa University Department of Hospital Pharmacy, School of Pharmacy, Kanazawa University
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- MIYAMOTO Ken-ichi
- Department of Hospital Pharmacy, University Hospital, Kanazawa University Department of Clinical Pharmacy, Graduate School of Natural Science and Technology, Kanazawa University Department of Medical Informatics, Graduate School of Medical Sciences, Kanazawa University Department of Hospital Pharmacy, School of Pharmacy, Kanazawa University
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Abstract
A retrospective analysis suggested that blood tacrolimus concentrations were consistent among patients with a body mass index (BMI) that was lean (<18.5), normal (≥18.5 and <25) or overweight/obese (≥25). The average maintenance dose of tacrolimus in patients with BMI ≥ 25 was significantly lower compared with that in patients with a BMI of less than 25. Lean and obese Zucker rats fed a normal diet were given tacrolimus intravenously or orally. The blood concentrations of tacrolimus in obese rats were significantly higher than those in lean rats after administration via both routes. The moment analysis has suggested that CLtot and Vdss of tacrolimus were not significantly different between lean and obese rats. The bioavailability was higher in obese rats, compared with that in lean rats. The protein expression of Cyp3a2 in the liver was significantly decreased in obese rats, compared with lean rats, while P-gp in the small intestine was also significantly decreased in obese rats. These results suggested that the steady-state trough concentration of tacrolimus in obese patients was well maintained by a relatively low dose compared with that in normal and lean patients, presumably due to increased bioavailability.
Journal
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- Drug Metabolism and Pharmacokinetics
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Drug Metabolism and Pharmacokinetics 29 (4), 341-347, 2014
The Japanese Society for the Study of Xenobiotics