TY - JOUR
T1 - Biliary excretion of imatinib mesylate and its metabolite CGP 74588 in humans
AU - Ramalingam, Sakkaraiappan
AU - Lagattuta, Theodore F.
AU - Egorin, Merrill J.
AU - Hayes, Michael J.
AU - Ramanathan, Ramesh K.
PY - 2004/9/4
Y1 - 2004/9/4
N2 - 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.
AB - 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.
KW - Biliary excretion
KW - CGP 74588
KW - Imatinib
KW - Liquid chromatography-mass spectometry
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U2 - 10.1592/phco.24.13.1232.38095
DO - 10.1592/phco.24.13.1232.38095
M3 - Article
C2 - 15460185
AN - SCOPUS:4344690687
SN - 0277-0008
VL - 24
SP - 1232
EP - 1235
JO - Pharmacotherapy
JF - Pharmacotherapy
IS - 9
ER -