米氮平的临床药物动力学。
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Timmer CJ、西尖JM Delbressine LP
米氮平的临床药物动力学。
Pharmacokinet。2000年6月,38 (6):461 - 74。doi: 10.2165 / 00003088-200038060-00001。
- PubMed ID
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10885584 (在PubMed]
- 文摘
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米氮平是第一个去和特定的含血清素的抗抑郁药(“NaSSA”)。很是迅速,从胃肠道吸收单个和多个口服后,和血浆浓度峰值达到2小时内。米氮平与血浆蛋白结合特异性的和可逆的方式(85%)。绝对生物利用度为50%左右,主要是因为肠道壁和肝初步的新陈代谢。米氮平显示线性药物动力学在15到80毫克的剂量范围。食品的存在率有轻微影响,但并不影响程度上,吸收。米氮平的药物代谢动力学情况是依赖于性别和年龄:女性和老年人血浆浓度高于男性和年轻的成年人。米氮平的消除半衰期范围从20到40小时,在协议时间达到稳定状态(4 - 6天)。从静脉全身间隙确定政府年轻男性31 L / h。肝脏和中度肾功能损害导致大约30%减少口服米氮平间隙; severe renal impairment causes a 50% decrease in clearance. There were no clinically or statistically significant differences between poor (PM) and extensive (EM) metabolisers of debrisoquine [a cytochrome P450 (CYP) 2D6 substrate] with regard to the pharmacokinetics of the racemate. The pharmacokinetics of mirtazapine appears to be enantioselective, resulting in higher plasma concentrations and longer half-life of the (R)-(-)-enantiomer (18.0 +/-2.5h) compared with that of the (S)-(+)-enantiomer (9.9+/-3. lh). Genetic CYP2D6 polymorphism has different effects on the enantiomers. For the (R)-(-)-enantiomer there are no differences between EM and PM for any of the kinetic parameters; for (S)-(+)-mirtazapine the area under the concentration-time curve (AUC) is 79% larger in PM than in EM, and a corresponding longer half-life was found. Approximately 100% of the orally administered dose is excreted via urine and faeces within 4 days. Biotransformation is mainly mediated by the CYP2D6 and CYP3A4 isoenzymes. Inhibitors of these isoenzymes, such as paroxetine and fluoxetine, cause modestly increased mirtazapine plasma concentrations (17 and 32%, respectively) without leading to clinically relevant consequences. Enzyme induction by carbamazepine causes a considerable decrease (60%) in mirtazapine plasma concentrations. Mirtazapine has little inhibitory effects on CYP isoenzymes and, therefore, the pharmacokinetics of coadministered drugs are hardly affected by mirtazapine. Although no concentration-effect relationship could be established, it was found that with therapeutic dosages of mirtazapine (15 to 45 mg/day), plasma concentrations range on average from 5 to 100 microg/L.
