Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 22, No 14S (July 15 Supplement), 2004: 2081
© 2004 American Society of Clinical Oncology

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Abstract

Intrapatient consistency of imatinib pharmacokinetics (PK) in patients (pts) with advanced cancers

University of Pittsburgh Cancer Institute, Pittsburgh, PA; Novartis Pharmaceuticals Corporation, East Hanover, NJ; National Cancer Institute/CTEP, Rockville, MD; Comp Cancer Ctr at Case Western Reserve University, Cleveland, OH

2081

Background: Imatinib (STI-571), approved for treatment of CML & GIST, is administered as daily PO therapy and is primarily metabolized by CYP3A. By analyzing PK data from pts receiving daily imatinib, we examined whether chronic dosing is associated with induction or impairment of imatinib clearance. Methods: 46 pts receiving daily imatinib (100–800 mg) for advanced cancers underwent intensive PK sampling on days 1 & 15. 20 pts had acceptable (NL) renal function (CL_Cr 60 mL/min). 26 pts had renal impairment (RI). Imatinib concentrations were quantitated by LC/MS. Plasma imatinib C x t data were modeled using non-compartmental methods. The elimination rate constant (k) was calculated using the plasma t1/2 (k=0.693/t1/2) & used to determine the accumulation index (1/1-e^-k), where is the dosing interval. Accumulation (d15 AUC/d1 AUC) was calculated for each pt & compared to the predicted accumulation index ratio. Results: There was large inter-pt variability in imatinib t1/2 & AUC on days 1 & 15 (table below). Except in 2 pts with severe RI, intra-pt variability in imatinib PK was small, as indicated by each pt's day 15 AUC agreeing well with that predicted by the accumulation index. Conclusions: Over 2 weeks of daily dosing, intra-pt imatinib PK was consistent. These data suggest sustained dosing is not associated with induction or impairment of imatinib clearance. Support: NCI No. N01-CO-12400, 2P30 CA47904, Novartis

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Abstract presentation from the 2004 ASCO Annual Meeting