Get access

Reaction phenotyping of vinblastine metabolism in dogs

Authors

  • S. Achanta,

    1. Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, USA
    Search for more papers by this author
    • Present address: Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA
  • L. K. Maxwell

    Corresponding author
    1. Department of Physiological Sciences, Center for Veterinary Health Sciences, Oklahoma State University, Stillwater, OK, USA
    • Correspondence address:

      264 McElroy Hall

      Physiological Sciences

      Stillwater

      OK 74078

      USA

      e-mail: lk.maxwell@okstate.edu

    Search for more papers by this author

Abstract

Vinblastine 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 cytochrome P450 enzyme is responsible for the majority of vinblastine metabolism in dogs. A panel of eight recombinant canine cytochrome P450 enzymes (CYP1A1, CYP1A2, CYP3A12, CYP3A26, CYP2B11, CYP2C41, CYP2C21 and CYP2D15) were incubated in vitro with vinblastine. Findings were confirmed by the use of canine polyclonal antibodies of cytochrome P450 enzymes (CYP1A1, CYP3A12, CYP2B11 and CYP2C21) that were pre-incubated with individual and pooled hepatic microsomes that were purified from canine liver. Substrate depletion was observed in the presence of recombinant CYP3A12, whereas depletion did not substantially occur when microsomes were pre-incubated with polyclonal antibodies against CYP3A12. These findings confirmed that CYP3A12 is the major cytochrome P450 isoform responsible for the metabolism of vinblastine in dogs.

Ancillary