Combined pharmacokinetic and urodynamic study of the effects of oral administration of phenylpropanolamine in female Beagle dogs

This study investigated the differences in pharmacokinetic, urodynamic and haemodynamic parameters in female Beagle dogs in which blood sampling and urethral pressure profiles were performed over 24 h periods, after single or three times daily (T0-T6h-T12h) administration of phenylpropanolamine (PPA). Maximal concentration (Cmax) was reached 2 h after PPA administration (Tmax). The half-life lasted 4 h and, because of bioaccumulation, three times daily administration induced an increase in Cmax. Compared to the control group, a significant increase in urethral resistance was observed at Tmax after 1 week of once daily administrations. After one week of administering PPA every 6 h during the daytime, but not during the night, and despite higher plasma concentrations, the urethral resistance did not increase at any time, compared to the control group. The increase in mean arterial pressure values was compensated by a decreased heart rate. The clinical efficacy of the temporary increase in urethral resistance following single daily administration of PPA in dogs suffering from urethral sphincter mechanism incompetence (USMI) needs to be further investigated in a randomised clinical trial.