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Pharmacokinetics of gemcitabine and its primary metabolite in dogs after intravenous infusion
Author(s) -
FREISE K. J.,
MARTÍNJIMÉNEZ T.
Publication year - 2006
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/j.1365-2885.2006.00726.x
Subject(s) - gemcitabine , pharmacokinetics , metabolite , pharmacology , active metabolite , volume of distribution , plasma concentration , bolus (digestion) , in vivo , chemistry , medicine , chemotherapy , biology , microbiology and biotechnology
Gemcitabine is a relatively new chemotherapeutic compound used to treat a variety of cancers in dogs. Previous work presented in a companion paper explored the plasma kinetics of gemcitabine and its inactive metabolite, 2′,2′‐difluorodeoxyuridine (dFdU), in dogs after an intravenous bolus gemcitabine dose and demonstrated the saturation of intracellular dFdCTP (2′,2′‐difluorodeoxycytidine 5′‐triphosphate) occurs in vitro with increasing extracellular gemcitabine exposure in canine melanoma cells. In this study, the plasma pharmacokinetics (PKs) of gemcitabine and dFdU are further explored after gemcitabine doses of 10, 30, and 60 mg/kg administered by intravenous infusion with a loading dose. Gemcitabine displayed linear PKs, while the kinetics of dFdU were not dose proportional. The overall clearance, volume of distribution at steady‐state, and terminal elimination half‐life ( t 1/2 ) for gemcitabine were 0.421 L/h·kg, 0.822 L/kg, and 1.49 h, respectively. Plasma concentrations of dFdU peaked at approximately 2 h postdosing and had a t 1/2 of 14.9 h.