Disposition of 6-chloro-2-pyridylmethyl nitrate, a new anti-anginal compound, in rats and dogs.
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 alpha and beta 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. beta-D-glucuronate (M4, 7%). No unchanged drug was excreted.
Terada
T
T
Research Laboratories, Fukisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Sakata
C
C
Ishibashi
K
K
Nakamura
T
T
Ishimura
R
R
Tsuchiya
T
T
Noguchi
H
H
D000787:Angina Pectoris / Q000188:drug therapy*; D000818:Animals; D001646:Bile / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D005243:Feces / Q000032:analysis; D008297:Male; D011725:Pyridines / Q000493:pharmacokinetics*; D051381:Rats; D013045:Species Specificity; D014018:Tissue Distribution
D011725:Pyridines; C056182:6-chloro-2-pyridylmethyl nitrate