Alpha-Amylase Inhibitor, CS-1036 Binds to Serum Amylase in a Concentration-Dependent and Saturable Manner

Abstract

(2R,3R,4R)-4-hydroxy-2-(hydroxymethyl)pyrrolidin-3-yl 4-O-(6-deoxy-b-D-glucopyranosyl)-a-D-glucopyranoside (CS-1036), which is an a-amylase inhibitor, exhibited biphasic and sustained elimination with a long t1/2 (18.4–30.0 hours) in rats and monkeys, but exhibited a short t1/2 (3.7–7.9 hours) in humans. To clarify the species differences in the t1/2, the plasma protein binding of CS-1036 was evaluated by ultrafiltration. A concentration-dependent and saturable plasma protein binding of CS-1036 was observed in rats and monkeys with the dissociation rate constant (KD) of 8.95 and 27.2 nM, and maximal binding capacity (Bmax) of 52.8 and 22.1 nM, respectively. By the assessments of the recombinant amylase and immunoprecipitation, the major binding protein of CS-1036 in rats was identified as salivary amylase (KD 5.64 nM). CS-1036 also showed concentration-dependent and saturable binding to huma