Pharmacokinetics and cellular uptake of imatinib and its main metabolite CGP74588
作者： Philipp le Coutre , Karl-Anton Kreuzer , Stefan Pursche , Malte v. Bonin , Traugott Leopold
DOI: 10.1007/S00280-003-0741-6
关键词: Imatinib 、 Leukemia 、 Pharmacokinetics 、 Myeloid leukemia 、 Medicine 、 Oral administration 、 Metabolite 、 Half-life 、 Pharmacology 、 Imatinib mesylate
摘要: Despite the remarkable clinical response rates to imatinib in treatment of bcr-abl leukemic patients, pharmacokinetic data on this relatively novel substance are needed improve our understanding emergence resistance, interindividual variations and biologic relevance its main metabolite N-desmethyl-imatinib. We present here obtained with a newly designed HPLC approach 97 patients chronic myeloid leukemia or acute lymphatic (ALL) under that allowed us calculate AUC (39.5 μg·h/ml for an oral dose 400 mg daily), t1/2 (18.2 h) peak concentration (1.92 μ/ml daily) plasma. In subgroup same parameters were analyzed also provide cerebrospinal fluid (CSF) ALL demonstrate administration resulted only marginal flux across blood-brain barrier. Finally, vitro setting, we determined cellular concentrations HL-60 cells showed over-proportional uptake both RPMI medium human Using arithmetical combining all imatinib-treated finally conclusive approximation basic
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