The study was conducted at the Michigan State University College of Veterinary Medicine. Sample analysis was performed at the Michigan State University Diagnostic Center for Population and Animal Health.
Pharmacokinetics and Relative Bioavailability of d-Penicillamine in Fasted and Nonfasted Dogs
Article first published online: 22 JUL 2013
Copyright © 2013 by the American College of Veterinary Internal Medicine
Journal of Veterinary Internal Medicine
Volume 27, Issue 5, pages 1071–1076, September/October 2013
How to Cite
Langlois, D.K., Lehner, A.F., Buchweitz, J.P., Ross, D.E., Johnson, M.B., Kruger, J.M., Bailie, M.B., Hauptman, J.G. and Schall, W.D. (2013), Pharmacokinetics and Relative Bioavailability of d-Penicillamine in Fasted and Nonfasted Dogs. Journal of Veterinary Internal Medicine, 27: 1071–1076. doi: 10.1111/jvim.12147
- Issue published online: 13 SEP 2013
- Article first published online: 22 JUL 2013
- Manuscript Accepted: 5 JUN 2013
- Manuscript Revised: 3 MAY 2013
- Manuscript Received: 30 JAN 2013
- Michigan State University College of Veterinary Medicine Companion Animal Fund
- Michigan State University College of Veterinary Medicine Trinket Fund
- Copper chelation;
- Copper toxicosis treatment;
- Copper-associated hepatitis
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.
Coadministration of d-penicillamine with food decreases relative bioavailability and maximum plasma drug concentrations (Cmax) in dogs.
Nine purpose-bred dogs with a median body weight of 17.0 kg.
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.
Two fasted dogs (22%) vomited after receiving d-penicillamine. Mean Cmax ± 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 Cmax in fed dogs (P < .001).
Conclusions and Clinical Importance
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.