Pharmacokinetics of imatinib mesylate in end stage renal disease. A case study.
OBJECTIVE
To evaluate the pharmacokinetics of imatinib mesylate (Glivec) and its main metabolite (CGP74588) in a patient with end stage renal disease on hemodialysis and compare it with published data from subjects with normal renal function.


METHODS
Serial blood samples were collected over a 2-weeks period in a patient who was receiving daily 400 mg oral imatinib mesylate for the treatment of a gastrointestinal stromal tumor metastatic to the liver while on hemodialysis. Plasma levels of imatinib and CGP74588 were determined by a liquid chromatography-tandem mass spectrometry assay.


RESULTS
The pharmacokinetic values for imatinib and CGP74588, respectively, were: maximum concentration (3,340 and 781 ng/ml), time to maximum concentration (2 h), half-life (18.2 and 34.0 h), area under the curve (53.9 and 14.8 microg.h/ml), and trough concentration (1,540 and 508 ng/ml) for at least 24 h. All obtained values fell within the range of values of imatinib and its metabolite obtained in patients with normal renal function. Dialysis courses were not found to intervene with plasma kinetics of the study drug.


CONCLUSIONS
Our results indicate that the pharmacokinetics of imatinib and its metabolite CGP74588 do not change in patients with end stage renal disease on hemodialysis. Thus, the standard dose of imatinib can be safely administered to patients on hemodialysis, and probably with renal failure, at any stage.
Pappas
Periklis
P
Department of Pharmacology, Medical School, University of Ioannina, 45110, Ioannina, Greece. ppappas@cc.uoi.gr
Karavasilis
Vasilis
V
Briasoulis
Evangelos
E
Pavlidis
Nicholas
N
Marselos
Marios
M
D000328:Adult; D000970:Antineoplastic Agents / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001549:Benzamides; D005260:Female; D006207:Half-Life; D006801:Humans; D000068877:Imatinib Mesylate; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000628:therapy; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D010879:Piperazines / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D011743:Pyrimidines / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D006435:Renal Dialysis
D000970:Antineoplastic Agents; D001549:Benzamides; C464561:CGP 74588; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate