Pharmacokinetics and first-pass effects of ε-acetamidocaproic acid after administration of zinc acexamate in rats

Zinc acexamate (ZAC) is ionized to zinc and ε-acetamidocaproic acid (AACA). Thus, the pharmacokinetics and tissue distribution of zinc and AACA after intravenous (50mg kg^-1) and oral (100mg kg^-1) administration of ZAC were evaluated in rats. Also the pharmacokinetics of AACA after intravenous (10, 20, 30, and 50mg kg^-1) and oral (20, 50, and 100mg kg^-1) administration of ZAC and the first-pass extractions of AACA at a ZAC dose of 20mg kg^-1 were evaluated in rats. After oral administration of ZAC (20mg kg^-1), approximately 0.408% of the oral dose was not absorbed, the F value was approximately 47.1%, and the hepatic and gastrointestinal (GI) first-pass extractions of AACA were approximately 8.50% and 46.4% of the oral dose, respectively. The incomplete F value of AACA was mainly due to the considerable GI first-pass extraction in rats. Affinity of rat tissues to zinc and AACA was lowthe tissue-to-plasma (T/P) ratios were less than unity. The equilibrium plasma-to-blood cells partition ratios of AACA were independent of initial blood ZAC concentrations of 1, 5, and 10g ml ^-1the mean values were 0.481, 0.490, and 0.499, respectively. The bound fractions of zinc and AACA to rat plasma were 96.6% and 39.0%, respectively.