title: Pharmacokinetics and relative bioavailability of D-penicillamine in fasted and nonfasted dogs.
abstract: BACKGROUND
  D-Penicillamine is the most commonly used copper-chelating agent in the treatment of copper-associated hepatitis in dogs. Response to therapy can be variable, and there is a lack of pharmacokinetic information available for dogs. Coadministering the drug with food to alleviate vomiting has been recommended for dogs, which contradicts recommendations for drug administration to humans.
  
  
  OBJECTIVE
  Coadministration of d-penicillamine with food decreases relative bioavailability and maximum plasma drug concentrations (C(max)) in dogs.
  
  
  METHODS
  Nine purpose-bred dogs with a median body weight of 17.0 kg.
  
  
  METHODS
  Dogs received D-penicillamine (12.5 mg/kg PO) fasted and with food in a randomized, crossover design. Blood samples were collected before and 0.25, 0.5, 1, 2, 3, 4, 8, 12, and 24 hours after dosing. Total d-penicillamine concentrations were measured using liquid chromatography coupled with tandem quadrupole mass spectrometry. Pharmacokinetic parameters were calculated for each dog.
  
  
  RESULTS
  Two fasted dogs (22%) vomited after receiving d-penicillamine. Mean C(max) ± standard deviation (SD) was 8.7 ± 3.1 μg/mL (fasted) and 1.9 ± 1.6 μg/mL (fed). Mean area under the plasma concentration curve ± SD was 16.9 ± 5.9 μg/mL·h (fasted) and 4.9 ± 3.4 μg/mL·h (fed). There were significant reductions in relative bioavailability and C(max) in fed dogs (P < .001).
  
  
  CONCLUSIONS
  Coadministration of d-penicillamine with food significantly decreases plasma drug concentrations in dogs. Decreased drug exposure could result in decreased copper chelation efficacy, prolonged therapy, additional cost, and greater disease morbidity. Administration of d-penicillamine with food cannot be categorically recommended without additional studies.
authors.affiliation: Department of Small Animal Clinical Sciences, College of Veterinary Medicine, East Lansing, MI.
authors.forename: D K
authors.initials: DK
authors.lastname: Langlois
authors.forename: A F
authors.initials: AF
authors.lastname: Lehner
authors.forename: J P
authors.initials: JP
authors.lastname: Buchweitz
authors.forename: D E
authors.initials: DE
authors.lastname: Ross
authors.forename: M B
authors.initials: MB
authors.lastname: Johnson
authors.forename: J M
authors.initials: JM
authors.lastname: Kruger
authors.forename: M B
authors.initials: MB
authors.lastname: Bailie
authors.forename: J G
authors.initials: JG
authors.lastname: Hauptman
authors.forename: W D
authors.initials: WD
authors.lastname: Schall
mesh_terms: D000818:Animals; D019540:Area Under Curve; D002614:Chelating Agents / Q000493:pharmacokinetics*; D004285:Dogs / Q000097:blood*; D005260:Female; D005508:Food Deprivation / Q000502:physiology*; D006207:Half-Life; D008297:Male; D010396:Penicillamine / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D002614:Chelating Agents; D010396:Penicillamine
keywords: Copper chelation; Copper toxicosis treatment; Copper-associated hepatitis