Present address: Kevin J. Freise, University of Iowa College of Pharmacy, Iowa City, IA 52242, USA.
Pharmacokinetics of gemcitabine and its primary metabolite in dogs after intravenous bolus dosing and its in vitro pharmacodynamics
Article first published online: 1 MAR 2006
Journal of Veterinary Pharmacology and Therapeutics
Volume 29, Issue 2, pages 137–145, April 2006
How to Cite
FREISE, K. J. and MARTÍN-JIMÉNEZ, T. (2006), Pharmacokinetics of gemcitabine and its primary metabolite in dogs after intravenous bolus dosing and its in vitro pharmacodynamics. Journal of Veterinary Pharmacology and Therapeutics, 29: 137–145. doi: 10.1111/j.1365-2885.2006.00725.x
- Issue published online: 1 MAR 2006
- Article first published online: 1 MAR 2006
- (Paper received 13 June 2005; accepted for publication 17 January 2006)
Gemcitabine is a chemotherapeutic agent used to treat a variety of cancers in humans and dogs. In this study, the plasma pharmacokinetics of gemcitabine and its inactive metabolite, 2′,2′-difluorodeoxyuridine (dFdU), were investigated in dogs after intravenous bolus gemcitabine doses of 3, 10, and 30 mg/kg. Furthermore, the intracellular accumulation of the active metabolite gemcitabine triphosphate, as a surrogate pharmacodynamic endpoint, was also determined in vitro in canine melanoma cells. Gemcitabine was characterized by linear kinetics, while dFdU dose proportionality remains unknown. The average gemcitabine clearance was 0.560 L/h·kg and volume of distribution at steady-state of 1.27 L/kg. The average terminal elimination half-life, depending on dose, ranged from 1.75 to 3.23 h. Plasma concentrations of dFdU peaked at approximately 2 h post-dosing. In vitro intracellular gemcitabine triphosphate accumulation was saturated with increasing extracellular gemcitabine concentrations. These data can be used to rationally design gemcitabine dosage regimes for canine oncology patients and as a basis for future investigations on the in vivo intracellular accumulation of gemcitabine triphosphate in dogs.