頁籤選單縮合
題 名 | The Role of the Cytochrome P450 System in the Metabolism of Psychotropic Drugs=細胞色素P450於精神藥物代謝之角色 |
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作 者 | 藍先元; 張文和; | 書刊名 | 臺灣精神醫學 |
卷 期 | 11:4 1997.12[民86.12] |
頁 次 | 頁3-14 |
分類號 | 418.21 |
關鍵詞 | 細胞色素P450; 藥物交互作用; 酵素抑制; 藥理遺傳學; Cytochrome P450; Drug interactions; Enzyme inhibition; Pharmacogenetics; |
語 文 | 英文(English) |
中文摘要 | 除了鋰鹽及羥化的benzodiazepine(如︰lorazepam、oxazepam以及temazepam)幾乎所有的精神藥物皆為親脂性化合物,它們必須先經細胞色素P450酵素代謝為極性較高的化合物,再經由結合作用(conjugation)而排出體外。細胞色素P450特性之一乃其酵素活性能夠被誘發或抑制。Quinidine、paroxetine、fluoxetine、norfluxetine及sertraline是細胞色素P450 2D6的強效抑制劑,因而能提昇多種傳統抗精神病藥物及三環抗鬱劑的血中濃度。Fluvoxamine乃P450 1A2的抑制劑,故與若干經由P450 1A2代謝之藥物(如clozapine及theophylline等)具有交互作用。反之,香煙中所含芳香族碳氫化合物則可誘發P450 1A2之活性。細胞色素P450 2C19是負責citalopram代謝之主要酵素;而propranolol之代謝乃由P450 2C19及2D6共同參與。Fluvoxamine、fluoxetine、sertraline及moclobemide皆可抑制2C19的活性。細胞色素P450 3A3/4負責最多種類藥物之代謝,包括carbamazepine、terfenadine、astemizole、alprazolam、triazolam、midazolam、以及其他多種benzodiazepines等。除了P450 1A2之外,3A3/4也負責clozapine部份的代謝。Clomipramine、imipramine及amitriptyline之代謝則是由P4501A2、2C19、2D6以及3A3/4所共同參與。葡萄柚汁、ketoconazole、erythromycin、cimetidine、verapamil、fluvoxamine、fluoxetine以及sertraline均可抑制P450 3A的活性。多種與藥物代謝相關之酵素具有顯著的種族差異;華人使用精神藥物的劑量以及所產生之療效或副作用常有別於其他人種。對於細胞色素P450各個成員各自的受質、誘發劑、及抑制劑的了解,有助於藥物交互作用之預測。此外,細胞色素P450所具有的基因多型性及種族差異可導致不同個體及種族間藥物代謝之重大歧異,這一點對於臨床醫療特具重要意義。 |
英文摘要 | Most psychotropic drugs are highly fat-soluble compounds that require metabolism by cytochrome P450 enzymes to more polar compounds prior to conjugation and elimination. An important characteristic of P450 cytochromes is that their enzymatic activities can be induced or inhibited. Quinidine, paroxetine, fluoxetine, norfluoxetine, and sertraline are potent inhibitors of P450 2D6 and have the potential of elevating the plasma concentration of many classical antipsychotics and tricyclic antidepressants. Cytochrome P450 1A2 is inhibited by fluvoxamine and is implicated in drug interactions with clozapine, theophylline, and others. In contrast, aryl hydrocarbon exposure from smoke can induce P450 1A2. P450 2C19 is responsible for the elimination of citalopram. Fluvoxamine, fluoxetine, sertraline, and moclobemide may inhibit the 2C19 system. P450 3A3/4 metabolizes carbamazepine, terfenadine, astemizole, alprazolam, triazolam, midazolam, and other benzodiazepines. In addition to P450 1A2, 3A3/4 also contributes to the elimination of clozapine. Clomipramine, imipramine, and amitriptyline are metabolized by P450 1A2, 2C19, 2D6, as well as 3A3/4. Grapefruit,juice, ketoconazole, erythromycin, cimetidine, verapamil, fluvoxamine, fluoxetine, and sertraline can all inhibit P450 3A's activity. The prominent differences of enzyme activities between Chinese and Caucasians are well documented, with great differences in the dosages, efficacy, and adverse effects of psychotropic drugs between different populations. Knowledge of the substrates, inducers, and inhibitors of cytochrome P450 isoenzymes assists in the prediction of clinically significant drug interactions. |
本系統中英文摘要資訊取自各篇刊載內容。