Reaction phenotyping of vinblastine metabolism in dogs

Abstract

AbstractVinblastine is a vinca alkaloid used either as a single agent or in combination therapy for the treatment of canine mast cell tumours and lymphomas. The objective of this study was to determine which isoform of cytochromeP450enzyme is responsible for the majority of vinblastine metabolism in dogs. A panel of eight recombinant canine cytochromeP450enzymes (CYP1A1,CYP1A2,CYP3A12,CYP3A26,CYP2B11,CYP2C41,CYP2C21andCYP2D15) were incubatedin vitrowith vinblastine. Findings were confirmed by the use of canine polyclonal antibodies of cytochromeP450enzymes (CYP1A1,CYP3A12,CYP2B11andCYP2C21) that were pre‐incubated with individual and pooled hepatic microsomes that were purified from canine liver. Substrate depletion was observed in the presence of recombinantCYP3A12, whereas depletion did not substantially occur when microsomes were pre‐incubated with polyclonal antibodies againstCYP3A12. These findings confirmed thatCYP3A12is the major cytochromeP450isoform responsible for the metabolism of vinblastine in dogs.