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One challenging aspect in the clinical development of molecularly targeted therapies, which represent a new and promising approach to treating cancers, has been the identification of a biologically active dose rather than a maximum tolerated dose. The goal of the present study was to identify a pharmacokinetic/pharmacodynamic relationship in preclinical(More)
PURPOSE The purpose of this study was to evaluate the effect of the receptor tyrosine kinase inhibitor SU11654 on the activity of its molecular target KIT in canine mast cell tumors (MCT) and correlate target inhibition with mutational status of the c-kit juxtamembrane domain and SU11654 plasma concentration. EXPERIMENTAL DESIGN Tumor biopsies were(More)
Baclofen is a racemic GABA(B) receptor agonist that has a number of significant pharmacokinetic limitations, including a narrow window of absorption in the upper small intestine and rapid clearance from the blood. Arbaclofen placarbil is a novel transported prodrug of the pharmacologically active R-isomer of baclofen designed to be absorbed throughout the(More)
PURPOSE To assess ibrutinib pharmacokinetics under fasted and fed conditions, impact of food-intake timing, and the safety and tolerability. METHODS Three studies were analyzed. Study 1 was a randomized, open-label, single-dose, four-way crossover study in 44 healthy participants. Study 2 was a randomized, repeat-dose crossover study in 16 patients with(More)
A simple device has been developed for serial venous blood sampling which permits the simultaneous measurement of locomotor activity in the freely moving rat. The device can be easily constructed from routine laboratory material and it does not interfere with the light beams used to measure locomotor activity. The device, in conjunction with an activity(More)
Ibrutinib (PCI-32765), a potent covalent inhibitor of Bruton's tyrosine kinase, has shown efficacy against a variety of B-cell malignancies. Given the prominent role of CYP3A in ibrutinib metabolism, effect of coadministration of CYP3A perpetrators with ibrutinib was evaluated in healthy adults. Ibrutinib (120 mg [Study 1, fasted], 560 mg [studies 2(More)
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