Pilanz Mechanism of Action

Pharmacology: Pharmacodynamics: Olanzapine is a thienobenzodiazepine which is second generation antipsychotics or atypical antipsychotics. Olanzapine has high affinity binding to serotonin receptors (5-HT_2A, 5-HT_2C and 5-HT₃), muscarinic receptors (M₁-M₅), histamine receptors (H₁), adrenergic receptors (α₁) and dopamine receptors (D₁-D₄). Although the precise mechanism of action in schizophrenia and bipolar disorder is not known, the efficiency of Olanzapine is thought to be mediated through combined antagonism of dopamine and serotonin type 2 receptor sites.
Pharmacokinetics: Absorption: Olanzapine is well absorbed following oral administration. The peak plasma Olanzapine concentrations occur in approximately 6 hours after oral doses (average : 5-8 hours). Food does not appear to affect the rate or the extent of GI absorption of the drug. The relative oral bioavailability of Olanzapine has been shown to be equivalent following administration of the conventional and orally disintegrating tablets of the drug.
Distribution: Distribution of Olanzapine, a highly lipophilic drug, into human tissue is extensive. The volume of distribution of Olanzapine has been reported to be approximately 1000 L. Olanzapine binds with protein in plasma(albumin and α₁-acid glycoprotein) for about 93%.
Metabolism: Olanzapine has extensive hepatic metabolism, partially via glucuronidation and cytochrome P450 (CYP1A2 and CYP2D6). The principal metabolites of Olanzapine are 10-N-glucuronide and 4'-N-desmethyl olanzapine. Both of these metabolites lack pharmacologic activity.
Elimination: About 57% of a dose is excreted in the urine, mainly as metabolites, and about 30% appears in the feces, respectively. Half-life elimination of Olanzapine is around 30 to 38 hours related to age, gender, and smoking. In adult, the apparent plasma clearance of Olanzapine ranges from 12 to 47 L/hour (mean : 25 L/hour). The clearance of Olanzapine in smoker is approximately 40% higher than in nonsmokers. The clearance of Olanzapine in females may be reduced by approximately 30% compared with males. In children and adolescents 10-18 years, the apparent plasma clearance at steady-state averaged 9.6 L/hour. The elimination half-life of orally administered Olanzapine is 1.5 times longer in healthy geriatric individuals 65years of age or older than in healthy younger adults. The pharmacokinetics of Olanzapine were similar in patients with severe renal impairment and healthy individuals, suggesting that dosage adjustment based upon the degree of renal impairment is not necessary. Although the presence of hepatic impairment would be expected to reduce the clearance of Olanzapine, a pharmacokinetic study evaluating the effect of impaired hepatic function in individuals with clinically important cirrhosis revealed little effect on the pharmacokinetics of Olanzapine.