Olanzapine-induced weight gain: chronic infusion using osmotic minipumps does not result in stable plasma levels due to degradation of olanzapine in solution.
The mechanisms underlying olanzapine-induced weight gain have not yet been fully elucidated. To examine the effects of long-term treatment with olanzapine on different aspects of energy balance, we administered olanzapine to male rats. Osmotic minipumps were chosen as preferred mode of administration because the half-life of olanzapine is only 2(1/2) h in rats compared to 30 h in humans. We discovered that, within one week, degradation of olanzapine occurred in the solution used to fill the minipump reservoir. This resulted in a decrease in delivered olanzapine and declining plasma levels over the course of the experiment. Therefore, we caution other researchers for the limitations of using osmotic minipumps to administer olanzapine for longer periods of time.
van der Zwaal
Esther M
EM
Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, University Medical Center Utrecht, The Netherlands.
Luijendijk
Mieneke C M
MC
Adan
Roger A H
RA
la Fleur
Susanne E
SE
D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D001569:Benzodiazepines / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004435:Eating / Q000187:drug effects; D015918:Infusion Pumps, Implantable; D008297:Male; D000077152:Olanzapine; D019999:Pharmaceutical Solutions; D051381:Rats; D017208:Rats, Wistar; D015430:Weight Gain / Q000187:drug effects*
D014150:Antipsychotic Agents; D019999:Pharmaceutical Solutions; D001569:Benzodiazepines; D000077152:Olanzapine