Vildagliptin was studied using an in situ rabbit intestinal perfusion technique. Vildagliptin absorptive clearance varied by site. Verapamil co-perfusion greatly improved vildagliptin absorption. Metformin co-perfusion had no effect on vildagliptin absorption.

AST-001 is a chemically synthesized inactive nitrogen mustard prodrug that is selectively cleaved to a cytotoxic aziridine (AST-2660) via aldo-keto reductase family 1 member C3 (AKR1C3). The purpose of this study was to investigate the pharmacokinetics and tissue distribution of the prodrug, AST-001, and its active metabolite, AST-2660, in mice, rats and monkeys. AST-001 has an acceptable pharmacokinetic profile, desirable efficacy and safety profile, as well as potential clinical efficacy, and is therefore currently well underway in clinical studies.

We described aging effects on the brain Aβ₄₀ and Aβ₄₂ peptide load and demonstrated that accumulation of the peptides in guinea pig (GP), whose genetic makeup and handling of Aβ peptides bear similarity to humans, was highly correlated with brain free cholesterol concentrations. With aging, brain Aβ peptides and free cholesterol concentrations were higher whereas protein expression levels of P-gp, Lrp1 and Cyp46a1 for Aβ peptide efflux and cholesterol metabolism, respectively, were reduced. Additionally, protein expression of Abca1 for cholesterol efflux was highly correlated to free cholesterol levels. These data suggest that the higher brain free cholesterol and reduced P-gp and Lrp1 play a role in Aβ peptide accumulation for the guinea pig.

VX-548 is a Nav 1.8 inhibitor that is undergoing clinical development for the treatment of acute pain. The current work demonstrated that VX-548 showed a gender difference in the pharmacokinetics in rats, which was ascribed to gender-biased hepatic metabolism.