Tubulin-dependent biochemical assay for the antineoplastic agent taxol and application to measurement of the drug in serum.
A biochemical assay for taxol with sensitivity to 0.1 microM has been developed. Taxol-dependent formation of tubulin polymers occurs at 37 degrees C in 1.0 M glutamate in the absence of GTP. These polymers are cold-stable and hydrolyze GTP at 0 degrees C, whereas tubulin alone will not hydrolyze the nucleotide in the cold. This assay has been used to follow rabbit serum levels of taxol injected iv. Although the drug appears to be almost totally protein-bound, it is nevertheless rapidly cleared from serum. The apparent alpha-phase and beta-phase half-lives after iv bolus administration in one rabbit are 2.7 and 42 mins, respectively.
D000470:Alkaloids / Q000097:blood*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000097:blood*; D002417:Cattle; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D017239:Paclitaxel; D011108:Polymers; D011817:Rabbits; D014404:Tubulin / Q000378:metabolism*
D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D011108:Polymers; D014404:Tubulin; D006160:Guanosine Triphosphate; D020558:GTP Phosphohydrolases; D017239:Paclitaxel