HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

Effect of chronic infusion of olanzapine and clozapine on food intake and body weight gain in male and female rats.

Abstract
Many antipsychotics cause weight gain in humans, but usually not in rats, when injected once or twice daily. Since blood antipsychotic half-lives are short in rats, compared to humans, chronic administration by constant infusion may be necessary to see consistent weight gain in rats. Male and female rats were implanted with mini-pumps for constant infusion of olanzapine (5 mg/kg/day), clozapine (10 mg/kg/day) or vehicle for 11 days. Food intake and body weight were measured; blood drug levels were measured by HPLC. Olanzapine increased food intake and body weight in female, but not male rats. Serum olanzapine concentrations were 30-35 ng/ml. Clozapine had no effect on food intake or body weight in female or male rats. Serum clozapine concentrations were about 75 ng/ml. Single-dose pharmacokinetic analysis revealed a serum terminal half-life of 1.2-1.5 h for each drug, with no sex differences. Despite the fact that olanzapine and clozapine promote weight gain in humans, these drugs appear to have minimal effects on body weight and food intake in rats, except for a modest effect of olanzapine in female rats, even though therapeutic levels of olanzapine are achieved in serum during chronic infusion. Hence, the rapid clearance of drug following single administration in previous studies cannot explain the weak or absent effects of antipsychotics on weight gain in this species. The rat thus appears to be an inadequate model of weight gain produced by some antipsychotics in humans.
AuthorsSuJean Choi, Briana DiSilvio, JayLynn Unangst, John D Fernstrom
JournalLife sciences (Life Sci) Vol. 81 Issue 12 Pg. 1024-30 (Sep 1 2007) ISSN: 0024-3205 [Print] England
PMID17822717 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Antipsychotic Agents
  • Benzodiazepines
  • olanzapine
  • Clozapine
Topics
  • Animals
  • Antipsychotic Agents (pharmacology)
  • Benzodiazepines (pharmacokinetics, pharmacology)
  • Clozapine (pharmacokinetics, pharmacology)
  • Eating (drug effects)
  • Female
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Weight Gain (drug effects)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: