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

• Published in: Xenobiotica Vol. 40; no. 7; pp. 485 - 498
• Main Authors: Choi, Y.H., Lee, U., Suh, J.H., Kim, Y.G., Choi, E.-Y., Oh, E., Lee, M.G.
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01-07-2010
• Subjects: Administration, Oral; Aminocaproates; Aminocaproic Acid - administration & dosage; Aminocaproic Acid - blood; Aminocaproic Acid - chemistry; Aminocaproic Acid - metabolism; Aminocaproic Acid - pharmacokinetics; Animals; Anti-Ulcer Agents - administration & dosage; Anti-Ulcer Agents - metabolism; Anti-Ulcer Agents - pharmacokinetics; Dose-Response Relationship, Drug; first-pass extraction; Molecular Structure; pharmacokinetics; Rats; Tissue Distribution; Zinc acexamate; ϵ-acetamidocaproic acid; ϵ-aminocaproic acid
• ISSN: 0049-8254; 1366-5928
• DOI: 10.3109/00498251003774745

Zinc acexamate (ZAC) is ionized to zinc and ϵ-acetamidocaproic acid (AACA). Thus, the pharmacokinetics and tissue distribution of zinc and AACA after intravenous (50 mg kg
−1
) and oral (100 mg kg
−1
) administration of ZAC were evaluated in rats. Also the pharmacokinetics of AACA after intravenous (10, 20, 30, and 50 mg kg
−1
) and oral (20, 50, and 100 mg kg
−1
) administration of ZAC and the first-pass extractions of AACA at a ZAC dose of 20 mg kg
−1
were evaluated in rats.
After oral administration of ZAC (20 mg 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 low-the 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 10 µg ml
−1
-the 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.