Pharmacology: Olanzapine is an antipsychotic agent that demonstrates a broad pharmacological profile across a number of receptor systems. It is a thienbenzodiazepine atypical antipsychotic. It has affinity for dopamine (D1, D2 and D4), histamine (H1), serotonin (5HT2A/2C) and adrenergic receptors.
Pharmacokinetics: Olanzapine is well-absorbed after oral administration, reaching peak plasma concentrations within 5-8 hrs. The absorption is not affected by food. Oral bioavailability relative to IV administration has not been determined. Olanzapine is metabolized in the liver by conjugative and oxidative pathways. The major circulating metabolite is the 10-N-glucuronide, which does not pass the blood-brain barrier. Cytochromes P-450-CYP1A2 and P-450-CYP2D6 contribute to the formation of the N-desmethyl and 2-hydroxymethyl metabolites, both exhibited significantly less in vivo pharmacological activity than olanzapine in animal studies. The predominant pharmacological activity is from the parent olanzapine.
After oral administration, the mean terminal elimination half-life of Olan in healthy subjects varied on the basis of age and gender. In healthy elderly, mean t½ is 51.8 hrs. In non-elderly subjects, the mean t½ is 33.8 hrs. In female versus male subjects, the mean elimination t½ was 36.7 hrs versus 32.3 hrs. In renally impaired patients (creatinine clearance <10 mL/min) versus healthy subjects, there was no significant difference in mean elimination half-life (37.7 versus 32.4) or drug clearance (21.2 vs 25 L/hr). A mass balance study showed that approximately 57% of radiolabeled olanzapine appeared in urine principally as metabolites.
The plasma clearance of Olan is lower in the elderly versus young subjects, in females versus males, and in nonsmokers versus smokers. However, the magnitude of the impact of age, gender, or smoking on olanzapine clearance and half-life is small in comparison to the overall variability between individuals.
The plasma protein-binding of olanzapine is about 93% over the concentration range of about 7-1000 ng/mL. Olan is bound predominantly to albumin and α1-acid glycoprotein.