2 0 0 0 OA 2-1 コロナ禍における薬学実務実習での工夫
1 0 0 0 OA 臨床薬理遺伝学と将来の薬物療法への展望
- 著者
- 有吉 範高
- 出版者
- 公益社団法人 日本薬理学会
- 雑誌
- 日本薬理学雑誌 (ISSN:00155691)
- 巻号頁・発行日
- vol.120, no.3, pp.181-186, 2002 (Released:2003-01-28)
- 参考文献数
- 23
ヒューマンゲノムプロジェクトの成果が今後の医療を大きく変革させると言われている.とりわけ医薬品に関わる業界へのインパクトは大きく,創薬のプロセスから臨床現場における薬剤の使い方に至るまで薬物に関わるおおよそ全ての過程が変貌するであろうと予想されている.文部科学省科学技術政策研究所·科学技術動向研究センターの技術予測調査によれば,2012年には個人個人の遺伝子の構造,一塩基多型(SNPs)等を含む全塩基配列が即座に安価で決定できるようになり,診断やオーダーメード治療に普及する,そうである.しかしながら薬物療法の現場において治療前にどのような遺伝子診断を行い,患者一人一人に最適な与薬を行うかという問題を,概念的にではなく現実問題として捉えた場合,技術の発展による診断法の進歩と低コスト化だけではおおよそ不充分である.インフォームドコンセントの在り方等倫理的な問題を含めた遺伝子診断体制の整備も無論急務ではあるが,もっとも重要と考えられることは臨床における充分なevidenceの蓄積である.すなわち与薬前に判定を行う遺伝子多型は,診断や薬物療法における有用性が確立されたものであり,真に患者のメリットになるものでなければならないのはもちろんのこと,遺伝子型にプラスして表現型に影響を及ぼす患者の年齢,病態,併用薬等を加味した上での投与設計がなされて始めて個人個人に最適化された薬物療法が達成できる.本稿では,遺伝因子が薬物療法において重要であるとの認識の出発点から,薬理遺伝学という学問領域の開花·発展の歴史を振返り,現状における問題点を通じて10年後(2012年)という近い将来の薬物療法への臨床薬理遺伝学の応用について展望してみたい.
1 0 0 0 OA CYP遺伝子多型解析の病棟業務への応用
- 著者
- 斉藤 嘉津彦 清水 瓊子 岡崎 正子 伊林 至洋 端 和夫 前野 康次郎 石井 清二 土橋 和文 島本 和明 戸田 貴大 黒澤 菜穂子 大和田 栄治 加藤 芳伸 大山 徹 梅津 有理 千田 道洋 有吉 範高 鎌滝 哲也 板谷 幸一
- 出版者
- 一般社団法人日本医療薬学会
- 雑誌
- 医療薬学 (ISSN:1346342X)
- 巻号頁・発行日
- vol.27, no.3, pp.228-234, 2001-06-10 (Released:2011-03-04)
- 参考文献数
- 11
- 被引用文献数
- 1 1
In recent years, genome science has undergone radical changes and numerous advances have led to the development of its use in medical practice. In particular developments in pharmacogenetics have demonstrated that genetic polymorphism is responsible for inter-individual differences in the drug metabolism. This study was conducted to identify the genetic polymorphisms of CYP 2C 9 and CYP 2 C19 using PCR-RFLP, and the application of a gene analysis was investigated in TDM or pharmaceutical management and in counseling services for patients. In a patient with the following pharmacokinetic parameters for phenytoin, for Km=6.69 μg/mL and Vmax = 3.62 mg/day/kg, and a largely decreased metabolic activity of CYP 2 C9 compared to the general population, the genetic differences in CYP 2 C9 could be determined in genomic DNA based on the patient's peripheral blood. Based on this finding, the effective dose for medication was calculated and administered to the patient. In addition, during medical consultations, both written and oral information in an easily comprehensible form could be given to patients with genetic polymorphism. These procedures allow a for the careful matching of the patient to the right medication and dose. This study indicates the possible application of a genetic analysis of CYP to “Evidence-Based Medicine” in the field of pharmaceutical management in order to control the dosage in individuals and to improve patient counseling.
1 0 0 0 OA CYP2A6の遺伝子多型に関する研究
- 著者
- 有吉 範高 布谷 憲一 高橋 由紀 宮本 昌美 醍醐 聡 梅津 有理 横井 毅 木村 寛三 Philippe BEAUNE 鎌滝 哲也
- 出版者
- The Japanese Society for the Study of Xenobiotics
- 雑誌
- 薬物動態 (ISSN:09161139)
- 巻号頁・発行日
- vol.15, no.1, pp.57-61, 2000 (Released:2007-03-29)
- 参考文献数
- 28
CYP2A6 has been characterized as a coumarin 7-hydroxylase in humans. A large interindividual difference in the activity of coumarin 7-hydroxylation suggested an existence of genetic polymorphism of this enzyme. In fact, CYP2A6*2 variant allele which has T→A substitution, leading to amino acid change from Leu160 to His160, has been found in Caucasian population as the most frequent mutation in poor metabolizers (PM) of coumarin. Although several drugs used clinically or under development such as fadrozole, losigamone and methoxyflurane are recognized at present to be good substrates of CYP2A6, no specific substrate of this CYP isoform has been known until we found a drug, SM-12502. In the phase I trial, 3 out of 28 Japanese subjects were classified as PM of the drug. In vitro studies demonstrated that CYP2A6 played a major role on the metabolism of the drug. Genomic analysis revealed that the PM phenotype was caused by the presence of a novel CYP2A6 gene variant which lacks the entire region of open reading frame encoding the enzyme in the PM. Thus, we designated the variant as “deletion-type” allele. We examined the frequency of individuals carrying homozygous deletion by a genotyping method established in our laboratory. Thus, the frequency was estimated to be 3-4% in Japanese. We found another CYP2A6 gene variant whose 60 bp in the 3'-untranslated region was substituted by the corresponding region of the CYP2A7 pseudogene. This variant was designated as “conversion-type” allele. We found that the allele frequency of the conversiontype was comparable to that of wild-type, CYP2A6*1 allele in Japanese. We also compared the frequency of the CYP2A6*2 allele as well as the deletion and the conversion alleles between Japanese and Caucasian. Consequently, a marked interracial difference in the frequency of the genetic variants of the CYP2A6 gene was observed. These results give an interesting insight into racial difference in response to drugs and evolution of the CYP2A gene subfamily in humans.
1 0 0 0 OA 簡易遺伝子診断法の開発・実臨床への適用による医薬品適正使用の推進
- 著者
- 有吉 範高
- 出版者
- 一般社団法人日本医療薬学会
- 雑誌
- 医療薬学 (ISSN:1346342X)
- 巻号頁・発行日
- vol.39, no.2, pp.61-76, 2013-02-10 (Released:2014-02-10)
- 参考文献数
- 39
Utilization of genetic information to achieve more appropriate use of drugs has not yet progressed, although a number of studies on the association between genetic polymorphisms and responses to drugs have been performed. Comparison among groups possessing different genotypes may give a significant difference in median responses to drugs, but little answer to the wide variation of drug response in patients sharing the same genotype. In fact, genetic information alone cannot accurately predict response to drugs in each individual.However, application of genetic information is often extremely useful to correct drug therapy to a more appropriate form in certain cases. Since pharmacists have to take responsibility for drug therapy in each patient, they should use all tools available including genotyping that may achieve better treatment. Nevertheless, since genetic information alone is insufficient to design better drug therapy in most cases at present, it is important to clarify factors, which should be considered together with genetic information. Clinical researches are indispensable to identify these factors.A simple genotyping method is a powerful tool to solve problems of drug therapy encountered at hospitals and/or to provide evidence through clinical studies on usefulness to apply genetic information to improve current drug therapy. The increase in the number of pharmacists, who are interested in not only drugs but also the genetic character of patients, is expected to contribute to better drug therapy in the future.