Influence of fluoxetine on olanzapine pharmacokinetics
Journal Title: The AAPS Journal - Year 2002, Vol 4, Issue 2
Abstract
Conventional antidepressant treatment fails for up to 30% of patients with major depression. When there are concomitant psychotic symptoms, response rates are even worse. Thus, subsequent treatment often includes combinations of antidepressants or augmentation with antipsychotic agents. Atypical antipsychotic agents such as olanzapine cause fewer extrapyramidal adverse effects than conventional antipsychotics; for that reason, they are an advantageous augmentation strategy for treatment-resistant and psychotic depression. The purpose of this study was to assess the potential for pharmacokinetic interaction between olanzapine and fluoxetine, a popular antidepressant that is a selective serotonin reuptake inhibitor. The pharmacokinetics of 3 identical single therapeutic doses of olanzapine (5 mg) were determined in 15 healthy nonsmoking volunteers. The first dose of olanzapine was taken alone, the second given after a single oral dose of fluoxetine (60 mg), and the third given after 8 days of treatment with fluoxetine 60 mg, qd. Olanzapine mean Cmax was slightly higher (by about 18%) and mean CL/F was slightly lower (by about 15%) when olanzapine was coadministered with fluoxetine in single or multiple doses. Olanzapine mean t1/2 and median tmax did not change. Although the pharmacokinetic effects of fluoxetine on olanzapine were statistically significant, the effects were small and are unlikely to modify olanzapines safety profile. The mechanism of influence is consistent with an inhibition of CYP2D6, which is known to control a minor pathway of olanzapine metabolism.
Authors and Affiliations
Denis Gossen, Jean-Marie de Suray, Francois Vandenhende, Claude Onkelinx, Diamon Gangji
Keywords
Related Articles
- EP ID EP682001
- DOI 10.1208/ps040209
- Views 69
- Downloads 0
Poly(ethylene glycol)-Modified Proteins: Implications for Poly(lactide-co-glycolide)-Based Microsphere Delivery
The reduced injection frequency and more nearly constant serum concentrations afforded by sustained release devices have been exploited for the chronic delivery of several therapeutic peptides via poly(lactide-co-glycoli...
The Challenges of Assessing Osteoarthritis and Postoperative Pain in Dogs
The challenge of measuring pain in veterinary medicine is compounded by the lack of fully validated, reliable methods to measure and assess pain in nonverbal patients. In human medicine, there are numerous, validated pai...
A Semi-mechanistic Model for the Effects of a Novel Glucagon Receptor Antagonist on Glucagon and the Interaction Between Glucose, Glucagon, and Insulin Applied to Adaptive Phase II Design
A potent novel compound (MK-3577) was developed for the treatment of type 2 diabetes mellitus (T2DM) through blocking the glucagon receptor. A semi-mechanistic model was developed to describe the drug effect on glucagon...
Human Cannabinoid 1 GPCR C-Terminal Domain Interacts with Bilayer Phospholipids to Modulate the Structure of its Membrane Environment
G protein-coupled receptors (GPCRs) play critical physiological and therapeutic roles. The human cannabinoid 1 GPCR (hCB1) is a prime pharmacotherapeutic target for addiction and cardiometabolic disease. Our prior biophy...
Intranasal Delivery of Proteins and Peptides in the Treatment of Neurodegenerative Diseases
The blood–brain barrier (BBB) is a major impediment to the therapeutic delivery of peptides and proteins to the brain. Intranasal delivery often provides a non-invasive means to bypass the BBB. Advantages of usin...