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Inhibitory Effect of Ketoconazole on the Pharmacokinetics of a Multireceptor Tyrosine Kinase Inhibitor BMS-690514 in Healthy Participants: Assessing the Mechanism of the Interaction with Physiologically-based Pharmacokinetic Simulations

BMS-690514, a selective inhibitor of the ErbB and vascular endothelial growth factor receptors, has shown antitumor activity in early clinical development. The compound is metabolized by multiple enzymes, with CYP3A4 responsible for the largest fraction (34%) of metabolism. It is also a substrate of P-glycoprotein (P-gp) in vitro. To assess the effect of ketoconazole on … Continued

Bioavailability of Intranasal vs. Rectal Diazepam

There remains an unmet medical need in the out-of-hospital management of seizure emergencies because older children and adults often refuse treatment with rectal gel due to social objections. We have previously reported that intranasal diazepam (DZP) administration is feasible, with maximum plasma concentrations (Cmax) and time to maximum concentration (Tmax) that are comparable to rectal DZP; but tolerability was poor. In … Continued

Pharmacokinetics, Pharmacodynamics, Physiologically-based Pharmacokinetic Modeling of Monoclonal Antibodies

Development of monoclonal antibodies (mAbs) and their functional derivatives represents a growing segment of the development pipeline in the pharmaceutical industry. More than 25 mAbs and derivatives have been approved for a variety of therapeutic applications. In addition, around 500 mAbs and derivatives are currently in different stages of development. mAbs are considered to be … Continued

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