Disposition of 6-chloro-2-pyridylmethyl nitrate, a new anti-anginal compound, in rats and dogs

Abstract

1. The absorption, distribution, metabolism and excretion of 6-chloro-2-pyridylmethyl nitrate, a new anti-anginal compound, were investigated in rats and dogs after intravenous and peroral administration of the ¹⁴C-labelled or unlabelled drug.

2. The half-lives of plasma levels for the α and β phase and systemic availability were 6 min, 42 min and 26–50% respectively in rats, and 8 min, 66 min and 5% respectively in dogs.

3. Radioactivity was rapidly distributed in the tissues of rats, and recovered mainly in the 0–24 h urine (95% of dose within 24 h) with no excretion in the expired air.

4. Several metabolites were detected on t.l.c. of rat and dog urine, and four were identified as N-(chloro-2-pyridylcarbonyl)-glycine (M1, 56%), N-acetyl-S-(6-chloro-2-pyridylmethyl)-L-cysteine (M2, 29%), 6-chloro-2-pyridinecarboxylic acid (M3, 5%) and 6-chloro-2-pyridylmethyl. β-D-glucuronate (M4, 7%). No unchanged drug was excreted.