Effect of absorption enhancers on the oral absorption of the GP IIB receptor antagonist, DMP-728, in rats and dogs
Burcham, DL; Aungst, BA; Hussain, M; Gorko, MA; Huang, SM; Et al
IPA COPYRIGHT: ASHP The effects of sodium caprate, palmitoylcarnitine chloride, and lauroylcholine chloride on the oral absorption of cyclic-(D-2-aminobutyryl-L-N2-methyl-L-arginylglycyl-L-aspartyl-3(aminomethyl)-benzoic acid), methane sulfonic acid salt (DMP-728), were studied in rats who received oral microcapsule formulations of 8 mg/kg drug and in dogs who received oral capsule formulations of 2 mg/kg drug. In rats, mean maximum concentration (Cmax) of DMP-728 was 0.07, 0.44, 0.44, and 0.43 mcg/ml for control, palmitoylcarnitine chloride, lauroylcholine chloride, and sodium caprate formulations, respectively. Mean area under the concentration time curve (AUC) values were 0.23, 1.38, 0.65, and 0.62 mcg h/ml, respectively. In dogs, mean Cmax was 0.21, 0.58, 0.25, 0.41, and 0.41 mcg/ml for the control, sodium caprate, enteric sodium caprate, palmitoylcarnitine chloride, and lauroylcholine chloride formulations, respectively. Mean AUC values were 0.7, 0.95, 0.71, 1.09, and 0.91, respectively. The palmitoyl carnitine chloride/lauroylcholine chloride study in dogs produced mean Cmax values of 0.15, 0.41 and 0.41 for the control, palmitoylcarnitine chloride, and lauroylcholine chloride, respectively. Mean AUC values were 0.58, 1.09, and 0.91, respectively.
