Gemcitabine degradation in whole blood from humans, dogs, cats, and horses

The purpose of this in vitro study was to compare the degradation of gemcitabine (2', 2'-difluorodeoxycytidine, dFdC), in Fresh Whole Blood (FWB) from humans, dogs, cats, and horses. A better understanding of the comparative degradation of gemcitabine may aid in the optimal design of therapeutic regimens in veterinary species. Fresh whole blood from humans, dogs, cats, and horses was spiked with dFdC and plasma was analyzed for dFdC and 2', 2'-difluorodeoxyuridine (dFdU) by high performance liquid chromatography. In these species, there was an initial rapid degradation of dFdC with a concomitant proportional increase in dFdU. Degradation of gemcitabine appeared similar in humans, dogs, and horses (p>0.05) whereas metabolism was slower in the cat than human (p=0.014), dog (p=0.010), or horse (p=0.0015). Based on these in vitro findings, dosing schemes for humans, dogs, and horses may be similar. In contrast, gemcitabine degradation occurred more slowly in the cat; this difference may dictate a different dosing scheme for optimal response in this species.