Disposition of cyproheptadine in cats after intravenous or oral administration of a single dose

Objective-To determine disposition of cyproheptadine hydrochloride in cats after intravenous or oral administration of a single dose. Animals-6 healthy cats. Procedure-A randomized crossover design was used, and each cat was studied after intravenous (2 mg) and oral (8 mg) administration of cyproheptadine. Blood samples were collected at fixed time intervals after drug administration, and serum cyproheptadine concentration was determined by means of polarized immunofluorescence. Results-Mean (+/- SD) residence time was significantly longer after oral (823 +/- 191 minutes) than after intravenous (339 +/- 217 minutes) administration, but no significant differences were detected between other pharmacokinetic parameters after oral and intravenous administration. Mean +/- SD oral bioavailability was 1.01 +/- 0.36. Mean elimination half-life after oral administration was 12.8 +/- 9.9 hours. Peak extrapolated cyproheptadine concentration was 669 +/- 206 ng/ml. Only 1 cat developed adverse effects (transient vocalization). Conclusions-Cyproheptadine appeared to be well tolerated in cats and had high bioavailability after oral administration. The mean elimination half-life of 12 hours indicated that approximately 2.5 days must elapse to achieve steady-state concentrations of cyproheptadine after oral administration of multiple doses. A 12-hour dosing interval is acceptable, but an 8-hour interval may be indicated for some cats. Clinical Relevance-On the basis of pharmacokinetic parameters determined in this study, the oral form of cyproheptadine appears to be suitable for use in clinical trials to treat anorexia in cats. Its half-life is compatible with once or twice daily dosing.