| Project/Area Number |
12672219
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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 |
応用薬理学・医療系薬学
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| Research Institution | Kumamoto University |
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Principal Investigator |
NAKAGAWA Kazuko Kumamoto University, Fxulty of Medical and Pharmaceutical Science, Associate Professor, 医学薬学研究部, 助教授 (20284747)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIZAKI Takashi Kumamoto University, Faculty of Medical and Pharmaceutical Science, Professor, 医学薬学研究部, 教授 (50158747)
安藤 正幸 熊本大学, 医学部, 教授 (00040204)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Type B adverse drug reactions / drug-induced pneumonia / anticonvulsants / drug-induced OT prolongation / risk factors / tegafur / drug metabolizing enzymes / TypeB adverse drug reaction / 遺伝的多型 / 診断方法 / 薬物代謝 / 呼吸器疾患 / リンパ球刺激試験 |
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| Research Abstract |
Objectives: Idiosyncratic or type B adverse drug reactions (type B ADR) are characterised by their unpredictability and lack of simple dose-dependency. They occur in a small proportion of patients, and usually the predisposing factors are unknown. We investigated the predisposing factors of type B ADR, seeking for a novel method for the diagnosis and prevention.
Methods: 1. We reviewed drug metabolizing enzymes and the genetic polymorphisms concerning 215 etiologic drugs in 795 cases with drug-induced pneumonia that had been colleded by a nation wide survey in Japan. 2. We assessed 1) the risk factors for type B ADR of anticonvulsants in 371 cases of epileptics, 2)the effects of psychotropic drugs on QT interval in 335 psychiatric inpatients and age- and sex-matched 335 controls, by using logistic regression analysis and/or nonlinear mixed-effect modeling. 3. We analyzed 5-FU/alpha-fluoro-beta-alanine in urine samples of 30 patients under tegafur therapy.
Results: 1. We developed a buccal smear sampling method (swab method) for ge notyping drug metabolizing enzyme genes in cases with type B ADR. 2. Carbamazepine (CBZ) dose and clearance, psychomotor retardation, tube feeding were identified as the risk factors for hyponatremia, leukopenia, and/or liver dysfunction. Pharmacokinetics of CBZ depended significantly on cytochrome P4503A5 genotypes but the relevance to the ADR under CBZ therapy is unknown. 3. Flunitrazepam was found to be a drug with the highest relative risk (RR=1.6, p<0.05) of the QT prolongation. 4. Urine 5-FU/alpha-fluoro-beta-alanine ration may be a potential marker of the susceptibility to tegafur toxicity.
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