Fluvoxamine對單一劑量Olanzapine藥物動力學之影響

The Effect of Fluvoxamine on the Single-dose Pharmacokinetics of Olanzapine

10.29478/TJP.200503.0006

楊雅旭(Ya-Hsu Yang)；邱智強(Chih-Chiang Chiu)；黃名琪(Ming-Chyi Huang)；劉慧卿(Hui-Ching Liu)；藍先元(Hsien-Yuan Lane)；張文和(Wen-Ho Chang)；盧孟良(Mong-Liang Lu)

藥物動力學 ； fluvoxamine ； olanzapine ； pharmacokinetics ； olanzapine ； fluvoxamine

台灣精神醫學

19卷1期（2005 / 03 / 01）

56 - 63

繁體中文

目的：Olanzapine是一種非典型的抗精神病藥物，主要經由cytochrome P450 (CYP) 1A2代謝，而fluvoxamine 是CYP的抑制劑，特別針對CYP1A2及CYP2C9，兩者併用可增加olanzapine的血漿濃度。本研究目的在比較使用fluvoxamine前後，單一劑量olanzapine藥物動力學變化。方法：10位精神分裂症病患，給予單一劑量 olanzapine 10mg後，於第0、0.5、1、1.5、2、2.5、3、4、5、6、8、10、12、24、36、48、60、72、96及120 小時收集靜脈血。在服用fluvoxamine l00mg/day 14天後，再以同樣方式抽血。以高效益相層析法分析 olanzapine血漿濃度，評估併用fluvoxamine對olanzapine藥物動力學變化的影響。結果：使用fluvoxamine 2週後，olanzapine的藥物動力學參數，呈現統計上顯著變化，包括尖峰藥物濃度由21.4±14.0 ng/mL升高為35.2±11.4ng/mL, 血漿濃度－時間曲線下面積(AUC(下標 0-120))由 823±480h•ng/mL升高為1202±504 h•ng/mL及 AUC(下標 0-∞)由910±499 h•ng/mL升高為1414±621h•ng/mL。清除率由13.0±4.60 L/h降低為8.01±2.55 L/h 和擬似分佈體積由 604±200 L降低為447±118 L。結論：本研究結果發現每天服用fluvoxamine 100mg確實可抑制單一劑量 olanzapine的代謝，影響相關藥物動力學參數。當olanzapine與fluvoxamine併用應小心監測藥物濃度及臨床反應。

Objective: Concomitant fluvoxamine may increase plasma levels of olanzapine via inhibition of cytochrome P450 1A2. The aim of the present study was to compare the pharmacokinetics of single-dose olanzapine before and after fluvoxamine administration in schizophrenic patients. Methods: Ten male schizophrenic patients were enrolled in this study. Each patient received a single 10mg dose of olanzapine on day l. A series of venous blood samples were obtained before olanzapine administration and 120 hours after treatment. Fluvoxamine 50 mg bid was administered from day 6 to day 20. On day 15, another single 10 mg dose of olanzapine was given. Venous blood samples were collected according to the same time schedule. Olanzapine was measured by high performance liquid chromatography with electronic detection. Results: The addition of fluvoxamine resulted in a significantly increased maximal plasma concentration of olanzapine (21.4±14.0 ng/mL vs. 35.2±11.4 ng/mL, p=0.0l3), area under the plasma concentration-time curve AUC(subscript (0-120) (823±480 h•ng/mL vs. 1202±504 h•ng/mL, p=0.005) and AUC(superscript 0-∞) (910±499 h•ng/mL vs. 1414±621 h•ng/mL, p=0.005) were noted. Concomitant reductions in clearance (13.0±4.60 L/h vs. 8.01±2.55 L/h, p=0.005) and volume of distribution (604±200 L vs. 447±118 L, p=0.017) were also found. Conclusions: The results of this study support that fluvoxamine can inhibit the metabolisms of olanzapine resulting in increased plasma level. Appropriate precautions should be taken to avoid toxicity when olanzapine and fluvoxamine are coadministered.

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