Olanzapine

Abstract

Multicentre trials in patients with schizophrenia confirm that olanzapine is a novel antipsychotic agent with broad efficacy, eliciting a response in both the positive and negative symptoms of schizophrenia. Compared with traditional antipsychotic agents, olanzapine causes a lower incidence of extrapyramidal symptoms and minimal perturbation of prolactin levels. Generally, olanzapine is well tolerated. The pharmacokinetics of olanzapine are linear and dose-proportional within the approved dosage range. Its mean half-life in healthy individuals was 33 hours, ranging from 21 to 54 hours. The mean apparent plasma clearance was 26 L/h, ranging from 12 to 47 L/h. Smokers and men have a higher clearance of olanzapine than women and nonsmokers. After administering [14C]olanzapine, approximately 60% of the radioactivity was excreted in urine and 30% in faeces. Olanzapine is predominantly bound to albumin (90%) and alpha 1-acid glycoprotein (77%). Olanzapine is metabolised to its 10- and 4'-N-glucuronides, 4'-N-desmethylolanzapine [cytochrome P450 (CYP) 1A2] and olanzapine N-oxide (flavin mono-oxygenase 3). Metabolism to 2-hydroxymethylolanzapine via CYP2D6 is a minor pathway. 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.

Comparison of Capillary and Venous Drug Concentrations After Administration of a Single Dose of Risperidone, Paliperidone, Quetiapine, Olanzapine, or Aripiprazole

“…Consequently, the times of sample collection were not optimal for a reliable calculation of pharmacokinetic parameters. The plasma concentrations observed in this study appeared to be consistent with published data for all evaluated drugs 25, 26, 27, 28, 29…”

Histological Study of the Effects of Olanzapine on the Liver of Adult Male Albino Rat with and without Vitamin C

“…It is metabolized extensively within the liver. Glucuronidation of Olanzapine is the major metabolic pathway [7] . By the help of liver enzymes other p450, mainly CYP2C8 help in its oxidative metabolism through catalysis of Olanzapine N-demethylation [8] .…”

Pediatric Olanzapine Intoxications and Plasma Exchange Application in One Case: Four Case Reports

“…Olanzapin düzeyinin maruziyet sonrası 11. saatte pik yapması aktif kömür uygulamasının yeterli dekontaminasyon oluşturamadığı şeklinde yorumlanabilir bununla birlikte DMO düzeyinin düşüşü ancak CYP1A2 inhibisyonu sonucunda olabilir. Olanzapinin sitokrom enzimleri üzerinde bilinen inhibitör ya da indükleyici etkisi bulunamamaktadır (7). Yatışından itibaren intravenöz sıvı tedavisi dışında tedavi verilmeyen hastada CYP1A2 üzerin-de gelişen bu inhibisyonun sebebi belirsizdir.…”