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題 名 | Fluvoxamine對Clozapine藥物動力學之影響=Effects of Fluvoxamine on Clozapine Pharmacokinetics |
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作 者 | 陳錦宏; 藍先元; 劉慧卿; 邱智強; 陳文慶; 張文和; | 書刊名 | 臺灣精神醫學 |
卷 期 | 12:2 1998.06[民87.06] |
頁 次 | 頁66-72 |
分類號 | 418.21 |
關鍵詞 | 藥物動力學; Pharmacokinetics; Clozapine; Clozapine-n-oxide; Desmethylclozapine; Fluvoxamine; |
語 文 | 中文(Chinese) |
中文摘要 | 目目的:比較精神病患者於使用fluvoxamine 2週前後,clozapine及其主要代謝物之單一劑量藥物動力學變化。方法:9位男性精神分裂症病患,於服用fluvoxamine 100 mg(50 mg 一天兩次)14天前後,分別給予口服單一劑量 50 mg clozapine,並分別於 0.5、1、1.5、2、2.5、3、4、5、6、8、10、12、24、36及48 小時後抽取靜脈血。以高效液相層析法檢測 clozapine 及其主要代謝物 desmethylclozapine(DMC)和clozapine N-oxide(CNO)之血漿濃度,並比較它們藥物動力學各項參數的變化。結果︰使用 fluvoxamine 2 週後,病人 clozapine 藥動學參數中,呈現明顯升高之達峰時間(T max)(由 2.66±2.51 hr升高為 4.55±2.51 hr, p=0.0006)、尖峰藥物濃度(C max)(由 73.1±22.2 ng/mL 升高為 109.5±31.5 ng/mL, p=0.004)及血漿濃度─時間曲線下面積(AUC)(由 780.8±259.6 ng/mL/hr 升為 2218.0±776.1 ng/mL/hr, p=0.0006)。而 DMC 及 CNO之 C max 值則有明顯下降,分別由 23.4±5.5 ng/mL 降為12.8±8.8 ng/mL(p=0.005)及 27.9±8.1 ng/mL 降為11.3±3.2 ng/mL(p=0.008)。結論︰本研究結果證實 fluvoxamine 可抑制 clozapine 代謝,增高 clozapine 血藥濃度,並影響相關藥物動力學參數。因此,當 clozapine 與 fluvoxamine 併用應小心監測血藥濃度及臨床反應。 |
英文摘要 | Objective: Interactions between fluvoxamine and clozapine may result in elevation of plasma clozapine levels following weeks of fluvoxamine treatment. The present study compare the pharmacokinetics of single-dose 50 mg clozapine before and after 14-day administration of fluvoxamine 50 mg b.i.d. in 9 schizophrenic male inpatients. Methods: The study was divided to two stages as follows: (1) On day 1, each patient received a single oral dose of 50 mg clozapine. Venous blood samples were obtained at 0.5、1、1.5、2、2.5、3、4、5、6、8、10、12、24、36 and 48 hours. (2) From day 3 to day 17, each patient tookfluvoxamine 50 mg b.i.d. On day 15, a single dose of 50 mg clozapine was taken again. Venous blood samples were obtained according to the same timetable of stage 1. The pharmacokinetics of clozapine and its two major metabolites were compared by paired t-test before and after administration of fluvoxamine. Result: After 2-week administration of fluvoxamine, a significantly higher AUC (780.8 ng/ml/hr vs. 2218.0 ng/ml/hr, p=0.0006), Tmax (2.66 hr vs. 4.55 hr, p=0.0006) and Cmax (73.1 ng/ml vs. 109.5 ng/ml, p=0.004), and lower clearance (0.060 L/hr vs. 0.019 L/hr, p=0.0007) of clozapine were found, while the Cmax of the major metabolites, desmethylclozapine and clozapine N-oxide, became lower (23.4 ng/m vs. 12.8 ng/ml, p=0.005; and 27.9 ng/m vs. 11.3 ng/ml, p=0.008). Conclusion: The results of this study lend support to previous suggestions that fluvoxamine, by inhibiting the activities of cytochrome P450 1A2 and 3A, could interfere with the metabolism of clozapine. Appropriate precautions should be taken to avoid toxicity when clozapine and fluvoxamine are coadministered. |
本系統中英文摘要資訊取自各篇刊載內容。