title: 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 (T(0),T(6h),T(12h)) administration of PPA. The maximal concentration (C(max)) was reached 2 h after PPA administration (T(max)) and the half-life (T((1/2))) was 4 h. Three times daily administration induced an increase in C(max) due to bioaccumulation. A significant increase in urethral resistance, compared to the control group, was observed at T(max) 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.
authors.affiliation: Department of Companion Animal Clinical Sciences B44, College of Veterinary Medicine, University of Liège, 4000 Liège, Belgium.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Noël
authors.forename: Carole
authors.initials: C
authors.lastname: Cambier
authors.forename: Kris
authors.initials: K
authors.lastname: Baert
authors.forename: Pascal
authors.initials: P
authors.lastname: Gustin
authors.forename: Raphael
authors.initials: R
authors.lastname: Denooz
authors.forename: Laurent
authors.initials: L
authors.lastname: Massart
authors.forename: Annick
authors.initials: A
authors.lastname: Hamaide
mesh_terms: D000284:Administration, Oral; D000316:Adrenergic alpha-Agonists / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D018592:Cross-Over Studies; D004285:Dogs / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D007700:Kinetics; D010665:Phenylpropanolamine / Q000097:blood / Q000493:pharmacokinetics*; D011897:Random Allocation; D014563:Urodynamics / Q000187:drug effects*
chemical_list: D000316:Adrenergic alpha-Agonists; D010665:Phenylpropanolamine