2005 Fiscal Year Final Research Report Summary
Pharmacokinetics of sedative medicine during brain hypothermia therapy and its proper use
| Project/Area Number |
16590113
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Medical pharmacy
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| Research Institution | University of Kagawa (2005)
The University of Tokushima (2004) |
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Principal Investigator |
HOUCHI Hitoshi University of Kagawa, University Hospital, Professor, 医学部附属病院, 教授 (00219156)
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| Co-Investigator(Kenkyū-buntansha) |
MINAKUCHI Kazuo University of Tokushima, University Hospital, Professor, 医学部・歯学部附属病院, 教授 (30284326)
HOSOI Eiji University of Tokushima, School of Medicine, Associated Professor, 医学部, 助教授 (70229186)
FUKUTA Yasushi University of Tokushima, Institute of Health Biosciences, Assistant Professor, 大学院・ヘルスバイオサイエンス研究部, 講師 (10294696)
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| Project Period (FY) |
2004 – 2005
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| Keywords | brain hypothermia therapy / sedative / midazolam / drug metabolizing enzyme / temperature dependence |
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| Research Abstract |
Control of sedation level is important during brain hypothermia therapy (BHT) that is expected to provide neuroprotection for severe brain injury. Hypothermia is known to induce some physiological changes. To gain the optimal sedation using midazolam during BHT, we examined the influence of hypothermia on pharmacokinetics of midazolam in patients undergoing BHT. During hypothermic period (33℃-35℃), total clearance of midazolam was decreased, resulting in that the half-life of serum disappearance of midazolam was prolonged and serum concentration was increased compared to when body temperature rose to 36℃. In some patients hepatic blood flow was reduced. Furthermore, in vitro study, Vmax value for metabolism of midazolam by CYP3A5 decreased to about 60% and 40% at 33℃ and 25℃, respectively, compared to that at 37℃. The value by CYP3A4 was decreased to 50% at 25℃, but not affected at 33℃. These results suggest that hypothermia induces the decrease of CYP3A5 activity and/or hepatic blood flow, which contributes to the increase of serum concentration of midazolam during hypothermic period.
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