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

Abstract

1. 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.

2. 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.

3. 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.

Keywords::

• Zinc acexamate
• ϵ-acetamidocaproic acid
• ϵ-aminocaproic acid
• pharmacokinetics
• tissue distribution
• first-pass extraction
• rats

Acknowledgements

This study was supported in part by a contract, ‘Pharmacokinetics of zinc acexamate’ from Kuhnil Pharmaceutical Company, Ltd., Seoul, South Korea.

Declartion of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.