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Pharmacological Studies with Vinblastine in the Dog¹

Departments of Pharmacology and Medicine [W. A. C., J. K., J. C. M.], and the Section of Comparative Medicine [A. S.], Yale University School of Medicine, New Haven, Connecticut 06510, and The Sterling Chemistry Laboratory [A. I. S., C. C. W.], Yale University, New Haven, Connecticut 06520

Tritiated vinblastine was prepared by catalytic exchange and its metabolism was studied in dogs. Plasma levels of drug fell in biphasic mode with initial and secondary phase half-lives of 17 to 38 min and 3 to 5 hr, respectively. Between 28.6 and 79.1% of plasma tritium was precipitable with cold trichloroacetic acid and thus was presumably protein bound. Blood leukocytes had levels of intracellular tritium between 2.4 and 11.8 times those of the coincident plasma samples. Over a 9-day period, urinary excretion accounted for 12.1 to 16.8% and fecal excretion accounted for 30.1 to 36.1% of the administered radioactivity. Ratios of biliary to plasma radioactivity varied between 7.3 and 56.9, with unchanged vinblastine being the major component (46.8 to 80.7%) in the bile.

¹ Supported by Grants CA 5138, CA 08341, CA 11095, and CA 12317 from the USPHS, as well as Grant DI 10H from the American Cancer Society.

² To whom requests for reprints should be addressed.

³ Currently a Faculty Research Associate of the American Cancer Society.

Received 10/28/74. Accepted 1/16/75.