PIII-18Validation of pharmacodynamic assessment method after administration of voglibose in healthy subjects

Abstract

BACKGROUND Voglibose is alpha-glucosidase inhibitor. Due to negligible oral absorption, measuring drug concentration in the blood is impractical. So we proposed the pharmacodynamic assessment method to reflect drug effect and this study aimed to validate this method. METHODS Placebo-controlled, selective two-period clinical study was conducted in 20 healthy male subjects. Period I: Subjects received a single oral dose of placebo on day 1. After 20 min of dosing, subjects had a 400 kcal sucrose-rich fluid meal. Blood samples for evaluation of serum glucose level were taken during 3 hours. On day 2, all procedures were the same as day 1 except administration of 0.3 mg voglibose instead of placebo. Period II: 9 subjects in whom considerable decreases of serum glucose level were observed in Period I participated in a multiple dose study (placebo: 8, 11 pm on day −1, and 9 am on day 1 / voglibose: 2, 8, 11 pm on day 1, and 9 am on day 2). RESULTS AUEC1h (area under the serum glucose level-time curve to 1h) slightly increased by 2.2% and Gmax(maximum serum glucose level) decreased by 0.5% with large intersubject variability when a single dose was administered. However, after multiple administration, the average percent decreases of AUEC1h and Gmax were 19.6% (P<0.001) and 22.2% (P<0.001), respectively. CONCLUSIONS Significant drug effects of voglibose in healthy subjects were revealed only after multiple doses. Changes of AUEC1h and Gmax compared to placebo may be alternative parameters to AUC and Cmax for equivalence study. Clinical Pharmacology & Therapeutics (2005) 79, P63–P63; doi: 10.1016/j.clpt.2005.12.226