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Reaction phenotyping of vinblastine metabolism in dogs
Author(s) -
Achanta S.,
Maxwell L. K.
Publication year - 2016
Publication title -
veterinary and comparative oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 34
eISSN - 1476-5829
pISSN - 1476-5810
DOI - 10.1111/vco.12084
Subject(s) - vinblastine , cyp1a2 , vinca alkaloid , microsome , cytochrome p450 , polyclonal antibodies , enzyme , vinca , biochemistry , isozyme , pharmacology , biology , metabolism , chemistry , antibody , immunology , chemotherapy , genetics , vincristine , cyclophosphamide
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.