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

Abstract

This study investigated the differences in pharmacokinetic, urodynamic and haemodynamic parameters after administration of two dosages of phenylpropanolamine (PPA) in female Beagle dogs. Blood was collected and urethral pressure profiles were performed over 24 h periods following single or three times daily (T0, T6h, T12h) administration of PPA. The maximal concentration (Cmax) was reached 2 h after PPA administration (Tmax) and the half-life (T1/2) was 4 h. Three times daily administration induced an increase in Cmax due to bioaccumulation. A significant increase in urethral resistance, compared to the control group, was observed at Tmax after 1 week of once daily administrations, but not when PPA was administered every 6 h during the day, despite higher plasma concentrations following more frequent dosing. An increase in mean arterial pressure was compensated by a decreased heart rate. Clinical efficacy with 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. © 2009 Elsevier Ltd. All rights reserved.