奥氮平。药代动力学和药效学。

文章的细节

引用

复制到剪贴板

卡拉汉JT, Bergstrom射频Ptak LR,比斯利厘米

奥氮平。药代动力学和药效学。

Pharmacokinet。1999年9月,37 (3):177 - 93。

PubMed ID

10511917 (在PubMed

]

文摘

精神分裂症患者的多中心临床试验中证实,奥氮平与广泛的功效,是一种新型抗精神病剂诱发响应的积极的和消极的精神分裂症的症状。与传统抗精神病药物相比,奥氮平引起锥体外系症状的发生率低和最小扰动的催乳素水平。一般来说,奥氮平是耐受性良好。奥氮平的药物代谢动力学情况是线性和dose-proportional批准的剂量范围内。它意味着在健康个体33小时,半衰期从21岁到54小时。表面等离子体间隙是26 L / h,从12到47 L / h。吸烟者和男性比女性有较高的奥氮平间隙和不吸烟者。管理[14 c]奥氮平后,大约60%的放射性排出的尿液和粪便的30%。奥氮平主要是绑定到白蛋白(90%)和α1-acid糖蛋白(77%)。奥氮平是生物新陈代谢的10 - 4“-N-glucuronides 4”-N-desmethylolanzapine(细胞色素P450 (CYP) 1 a2)和奥氮平N-oxide(黄素mono-oxygenase 3)。CYP2D6 2-hydroxymethylolanzapine通过新陈代谢是次要的途径。 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.

beplay体育安全吗DrugBank数据引用了这篇文章

药物酶

药物	酶	类	生物	药理作用	行动
奥氮平	细胞色素P450 1 a2	蛋白质	人类	没有	底物	细节
奥氮平	细胞色素P450 2 d6	蛋白质	人类	没有	底物 抑制剂	细节
奥氮平	二甲基苯胺单氧酶(N-oxide-forming) 3	蛋白质	人类	未知的	底物	细节

药物载体

药物	航空公司	类	生物	药理作用	行动
奥氮平	Alpha-1-acid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