2014 Fiscal Year Final Research Report
Influence of body mass index change on pharmacokinetics in clinical practice
| Project/Area Number |
24790149
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Medical pharmacy
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | BMI / 肥満 / タクロリムス / シクロスポリン / 薬物動態変動 / 個別化医療 / 投与設計 / バイオアベイラビリティー |
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| Outline of Final Research Achievements |
We found that the dose-normalized steady-state trough concentration ratio of orally administered tacrolimus in blood is increased in obese patients with a body mass index (BMI) over 25 compared with other patients having normal and lower BMI. In order to clarify the mechanisms involved in this increase, we examined the influence of obesity on tacrolimus pharmacokinetics using genetically obese model rats. Rats (18 weeks of age) were given tacrolimus intravenously or orally. The blood concentrations of this drug in obese rats were higher than those in lean rats after administration via both routes. The bioavailability of tacrolimus was significantly increased in obese rats compared with lean rats. Protein expression of P-glycoprotein in the small intestine was significantly decreased in obese rats. These results indicate that the high blood concentration of tacrolimus in obese patients is presumably a consequence of increased tacrolimus bioavailability.
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| Free Research Field |
薬物動態学
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