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題 名 | 併用Fluvoxamine對Clozapine穩態血漿濃度之影響=Effect of Concomitant Fluvoxamine on Steady-state Plasma Clozapine Concentrations in Schizophrenic Patients |
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作 者 | 陳坤波; 盧孟良; 藍先元; 張文和; | 書刊名 | 臺灣精神醫學 |
卷 期 | 13:3 1999.09[民88.09] |
頁 次 | 頁43-51 |
分類號 | 418.21 |
關鍵詞 | 藥物動力學; Pharmacokinetics; Clozapine; Clozapine-N-oxide; N-desmethylclozapine; Fluvoxamine; Desmethylclozapine; |
語 文 | 中文(Chinese) |
中文摘要 | 目的:本研究之目的在於探討併用fluvoxamine及低劑量clozapine(100 mg/day)四 週,對於穩定狀態clozapine血漿濃度之影響。方法:20位精神分裂症患者接受clozapine 100 mg/day 14天後,及併用fluvoxamine 50 mg/day 28天後,接受靜脈血採樣,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。結果:患者clozapine血漿濃度之基礎值較高加索人高出50-100%。併用fluvoxamine 28 天後,clozapine及DMC血漿濃度顯著上昇(clozapine:187.4±98.7 ng/ml vs. 426.6±208.5 ng/ml, p<0.001; DMC: 76.9±39.8 ng/ml vs. 134.7±54.6 ng/ml, p<0.001),CNO血漿濃度維持不變。 在相同clozapine劑量下,東方人的clozapine血漿濃度顯著高於高加索人,因此東方人每天 給予200-300 mg clozapine便可以達到適當治療濃度。併用fluvoxamine四週後,clozapine及 DMC血漿濃度分別有2.5倍及2倍的增加。此結果可能是CYP3A4、CYP2C19及CYP1A2 受到抑制所造成。當clozapine與fluvoxamine併用時,對clozapine血中濃度及臨床反應需 特別小心監測。結論:低劑量clozapine (100 mg/day)與fluvoxamine (50 mg/day)併用,即可 達到clozapine有效治療之血漿濃度,從而大幅降低治療成本。 |
英文摘要 | Object: Clozapine is the substrate of various cytochrome P450 isoenzymes, including 1A2, 2C9, 2C19, and 3A4. Fluvoxamine is the inhibitor of these isoenzymes. The study prospectively investigated the effects of fluvoxamine on clozapine metabolism in schizophrenic patients under steady state conditions. Methods: Twenty treatment-refractory schizophrenic patients were treated with clozapine at a fixed dose of 100 mg/day for 14 days. Fluvoxamine 50 mg/day was then added to the clozapine regimen. Plasma concentrations of clozapine and its two metabolites, N- desmethylcozapine (DMC) and clozapne N-ox-ide(CNO), were measured prior to and after 28 days of fluvoxamine coadministration. The plasma levels of clozapine, DMC, and CNO were measured by ultraviolet high performance liquid chromatography. Results: The mean trough plasma concentrations of clozapine and DMC were markedly elevated after 28 days of fluvoxamine coadministration (clozapine: 187.4±98.7 vs. 426.6±208.5 ng/mL; DMC: 76.9±39.8 vs. 134.7± 54.6 ng/mL), whereas CNO concentrations remained unchanged (25.4±11.7 vs. 25.9±11.6 ng/mL). The DMC /clozapine (0.44±0.15 vs. 0.35±0.13)and CNO clozapine ratios (0.15±0.09 vs. 0.07± 0.05) were significantly decreased after 28 days of combined treatment. Conclusion: Low dose clozapine-fluvoxamine coadministration increased the clozapine level by a factor of 2.5, whereas only a two-fold increase in the DMC levels occurred. The finding of inhibitory effects of fluvoxamine on clozapine metabolism after 4 weeks of therapy suggests that this combination may provide effective long-term inhibition of clozapine metabolism. Provided that the metabolic profiles of clozapine are measured regularly to monitor the inhibitory effects of fluvoxamine, this combination could theoretically be a safe and efficacious therapy with the potential to achieve substantial cost reduction. (Full Text in Chinese) |
本系統中英文摘要資訊取自各篇刊載內容。