title: Posaconazole pharmacokinetics after administration of an intravenous solution, oral suspension, and delayed-release tablet to dogs.
abstract: OBJECTIVE
  To determine pharmacokinetics of posaconazole in dogs given an IV solution, oral suspension, and delayed-release tablet.
  
  
  METHODS
  6 healthy dogs.
  
  
  METHODS
  Posaconazole was administered IV (3 mg/kg) and as an oral suspension (6 mg/kg) to dogs in a randomized crossover study. Blood samples were collected before (time 0) and for 48 hours after each dose. In an additional experiment, 5 of the dogs received posaconazole delayed-release tablets (mean dose, 6.9 mg/kg); blood samples were collected for 96 hours. Plasma concentrations were analyzed with high-performance liquid chromatography.
  
  
  RESULTS
  IV solution terminal half-life (t1/2) was 29 hours (coefficient of variation [CV], 23%). Clearance and volume of distribution were 78 mL/h/kg (CV, 59%) and 3.3 L/kg (CV, 38%), respectively. Oral suspension t1/2 was 24 hours (CV, 42%). Maximum plasma concentration (Cmax) of 0.42 μg/mL (CV, 56%) was obtained at 7.7 hours (CV, 92%). Mean bioavailability was 26% (range, 7.8% to 160%). Delayed-release tablet t1/2 was 42 hours (CV, 25%), with a Cmax of 1.8 μg/mL (CV, 44%) at 9.5 hours (CV, 85%). Mean bioavailability of tablets was 159% (range, 85% to 500%). Bioavailability of delayed-release tablets was 497% (range, 140% to 1,800%) relative to that of the oral suspension.
  
  
  CONCLUSIONS
  Absorption of posaconazole oral suspension in dogs was variable. Absorption of the delayed-release tablets was greater than absorption of the oral suspension, with a longer t1/2 that may favor its clinical use in dogs. Administration of delayed-release tablets at a dosage of 5 mg/kg every other day can be considered for future studies.
authors.affiliation: Department of Molecular Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kendall
authors.forename: Mark G
authors.initials: MG
authors.lastname: Papich
mesh_terms: D061605:Administration, Intravenous / Q000662:veterinary; D000284:Administration, Oral; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000493:pharmacokinetics; D004285:Dogs / Q000378:metabolism*; D005260:Female; D006207:Half-Life; D008297:Male; D013535:Suspensions / Q000008:administration & dosage / Q000493:pharmacokinetics; D013607:Tablets / Q000008:administration & dosage / Q000493:pharmacokinetics; D014230:Triazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000935:Antifungal Agents; D003692:Delayed-Action Preparations; D013535:Suspensions; D013607:Tablets; D014230:Triazoles; C101425:posaconazole