Lower mean weight after 14 days intravenous administration peptide YY3-36 (PYY3-36) in rabbits.

OBJECTIVE

Endogenous peptide YY(3-36) (PYY(3-36)) is associated with postprandial regulation of appetite. We investigated the safety and effectiveness of peripherally administered synthetic human PYY(3-36) for 14 days in New Zealand white rabbits. Weight gain and food consumption were assessed and pharmacokinetics and toxicity characterized.

RESEARCH METHODS AND PROCEDURES: In all, 24 animals were randomized to one of four intravenous treatment groups - control (0.9% saline) or PYY(3-36) bolus at 4.1, 41.0, or 205 microg/kg/day. Body weight and consumption of fixed food allotment were measured daily. Hematology and serum chemistries were profiled at baseline and Day 15, and pharmacokinetics measured following dose 14. Histopathologic examination of designated tissues and organs in control and PYY(3-36) 205 mug/kg animals was conducted. All animals were subject to clinical and macroscopic observation.

RESULTS

The trend effect of higher dose PYY(3-36) on lower average weight was significant (P = 0.01; Day 14 compared to baseline) and its effect on reduced food consumption was suggested (P = 0.065; number of days < or =75% food eaten, compared with control). Hematology and clinical chemistries were within normal limits pretest and at Day 15. No clinical, macroscopic, histologic, or microscopic changes related to the test article were observed over the course of study.

DISCUSSION: Lower average weight occurs in rabbits treated once daily with intravenous injection PYY(3-36) (205 microg/kg/day) over 14 days. No clinical or histologic signs of toxicity were observed. Further research is warranted to describe alternate routes of peripheral administration for optimizing weight control.