Biliary excretion of imatinib mesylate and its metabolite CGP 74588 in humans

Sakkaraiappan Ramalingam, Theodore F. Lagattuta, Merrill J. Egorin, Michael J. Hayes, Ramesk K Ramanathan

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1232-1235
Number of pages4
JournalPharmacotherapy
Volume24
Issue number9
DOIs
StatePublished - Sep 4 2004
Externally publishedYes

Fingerprint

Liver Function Tests
Cytochrome P-450 CYP3A
Gastrointestinal Stromal Tumors
Imatinib Mesylate
Hepatobiliary Elimination
CGP 74588
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Bile
Liquid Chromatography
Stents
Mass Spectrometry
Therapeutics
Renal Elimination

Keywords

  • Biliary excretion
  • CGP 74588
  • Imatinib
  • Liquid chromatography-mass spectometry

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Biliary excretion of imatinib mesylate and its metabolite CGP 74588 in humans. / Ramalingam, Sakkaraiappan; Lagattuta, Theodore F.; Egorin, Merrill J.; Hayes, Michael J.; Ramanathan, Ramesk K.

In: Pharmacotherapy, Vol. 24, No. 9, 04.09.2004, p. 1232-1235.

Research output: Contribution to journalArticle

Ramalingam, Sakkaraiappan ; Lagattuta, Theodore F. ; Egorin, Merrill J. ; Hayes, Michael J. ; Ramanathan, Ramesk K. / Biliary excretion of imatinib mesylate and its metabolite CGP 74588 in humans. In: Pharmacotherapy. 2004 ; Vol. 24, No. 9. pp. 1232-1235.
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