Biliary excretion of imatinib mesylate and its metabolite CGP 74588 in humans.
Imatinib mesylate, licensed to treat chronic myelogenous leukemia and gastrointestinal stromal tumors, is metabolized by cytochrome P450 3A and undergoes little renal excretion, but its biliary excretion by humans is uncharacterized. Liquid chromatography-mass spectrometry was used to quantitate imatinib and its metabolite CGP 74588 in the bile of two patients with biliary stents; the ratio of imatinib:CGP 74588 in each was approximately 9:1. In the first patient, who was receiving long-term therapy with imatinib 400 mg/day and had normal liver function tests, biliary imatinib accounted for 17.7% of the daily dose and CGP 74588 accounted for 2.1%. In the second patient, who had elevated liver function tests and was studied after his first dose of imatinib 300 mg, biliary imatinib accounted for only 1.8% of the daily dose and CGP 74588 accounted for 0.2%. These data show both the qualitative similarities and the quantitative variability in biliary excretion of imatinib and its principal metabolite.
Divison of Hemotology/Oncology, Deparatment of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Sakkaraiappan
S
Ramalingam
Theodore F
TF
Lagattuta
Merrill J
MJ
Egorin
Michael J
MJ
Hayes
Ramesh K
RK
Ramanathan
D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000970:Antineoplastic Agents / Q000378:metabolism / Q000627:therapeutic use*; D001549:Benzamides; D001646:Bile / Q000737:chemistry*; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy*; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000302:isolation & purification* / Q000378:metabolism / Q000627:therapeutic use*; D011743:Pyrimidines / Q000302:isolation & purification* / Q000378:metabolism / Q000627:therapeutic use*; D015607:Stents
D000970:Antineoplastic Agents; D001549:Benzamides; C464561:CGP 74588; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate