奥氮平。药代动力学和药效学概况。

文章的细节

引用

复制到剪贴板

卡拉汉JT，伯格斯特罗姆RF，普塔克LR，比斯利CM

奥氮平。药代动力学和药效学概况。

临床药效学杂志1999 Sep;37(3):177-93。

PubMed ID

10511917 (PubMed视图

］

摘要

精神分裂症患者的多中心试验证实，奥氮平是一种具有广泛疗效的新型抗精神病药物，对精神分裂症的阳性和阴性症状都有反应。与传统的抗精神病药物相比，奥氮平引起锥体外系症状的发生率较低，泌乳素水平的扰动最小。一般来说，奥氮平耐受性良好。在批准的剂量范围内，奥氮平的药代动力学呈线性和剂量成正比关系。它在健康个体中的平均半衰期为33小时，从21小时到54小时不等。平均血浆表观清除率为26 L/h，范围为12 ~ 47 L/h。吸烟者和男性比女性和非吸烟者有更高的奥氮平清除率。在给予[14C]奥氮平后，大约60%的放射性物质随尿液排出，30%随粪便排出。奥氮平主要结合白蛋白(90%)和α - 1-酸性糖蛋白(77%)。奥氮平代谢为10-和4'- n -葡萄糖苷，4'- n -去甲基奥氮平[细胞色素P450 (CYP) 1A2]和奥氮平n -氧化物(黄素单加氧酶3)。通过CYP2D6代谢为2-羟甲基奥氮平是一个次要途径。 The 10-N-glucuronide is the most abundant metabolite, but formation of 4'-N-desmethylolanzapine is correlated with the clearance of olanzapine. Olanzapine does not inhibit CYP isozymes. No clinically significant metabolic interactions were found between olanzapine and diazepam, alcohol (ethanol), imipramine, R/S-warfarin, aminophylline, biperiden, lithium or fluoxetine. Fluvoxamine, an inhibitor of CYP1A2, increases plasma concentrations of olanzapine; inducers of CYP1A2, including tobacco smoke and carbamazepine, decrease olanzapine concentrations. Orthostatic changes were observed when olanzapine and diazepam or alcohol were coadministered. Pharmacodynamic interactions occurred between olanzapine and alcohol, and olanzapine and imipramine, implying that patients should avoid operating hazardous equipment or driving an automobile while experiencing the short term effects of the combinations. Individual factors with the largest impact on olanzapine pharmacokinetics are gender and smoking status. The plasma clearance of olanzapine generally varies over a 4-fold range, but the variability in the clearance and concentration of olanzapine does not appear to be associated with the severity or duration of adverse effects or the degree of efficacy. Thus, dosage adjustments appear unnecessary for these individual factors. However, dosage modification should be considered for patients characterised by a combination of factors associated with decreased oxidative metabolism, for example, debilitated or elderly women who are nonsmokers.

引用本文的药物库数据

药物酶

药物	酶	种类	生物	药理作用	行动
奥氮平	细胞色素P450 1A2	蛋白质	人类	没有	底物	细节
奥氮平	细胞色素P450 2D6	蛋白质	人类	没有	底物 抑制剂	细节
奥氮平	二甲基苯胺单加氧酶[n -氧化物形成	蛋白质	人类	未知的	底物	细节

药物载体

药物	航空公司	种类	生物	药理作用	行动
奥氮平	-1-酸性糖蛋白1	蛋白质	人类	没有	粘结剂	细节
奥氮平	血清白蛋白	蛋白质	人类	没有	粘结剂	细节