PT  - JOURNAL ARTICLE
AU  - B. D. CAMERON
AU  - L. F. CHASSEAUD
AU  - D. R. HAWKINS
AU  - J. D. LEWIS
TI  - THE RADIOSYNTHESIS, PERCUTANEOUS ABSORPTION, AND METABOLISM OF THE WOUND-HEALING AGENT CALCIUM ACEXAMATE IN ThE RAT
DP  - 1974 Sep 01
TA  - Drug Metabolism and Disposition
PG  - 416--423
VI  - 2
IP  - 5
4099  - http://dmd.aspetjournals.org/content/2/5/416.short
4100  - http://dmd.aspetjournals.org/content/2/5/416.full
SO  - Drug Metab Dispos1974 Sep 01; 2
AB  - [2-14C]Caprolactam, prepared from [1-14C]cyclohexanone by reaction with sodium azide, was acetylated and ring-cleaved to give N-acetyl-6-amino[1-14C]hexanoate (acexamic acid) as the calcium salt. At least 70% of a single oral dose of calcium 14C-acexamate was rapidly absorbed by rats and almost eliminated in 48 hr. During 4 days, a mean of 68.6% was excreted in the urine, 15.2% in the feces, and 0.9% in the expired air as 14CO2, and 1.8% remained in the carcass and viscera. In the urine and feces, 57.0 and 13.8% of the dose, respectively, consisted of unchanged acexamate and less than 4% of 6-aminohexanoic acid. After the oral dose, plasma concentrations of 14C, probably consisting mainly of unchanged acexamate, were highest after 1 hr and declined with a half-life of 4 hr. After an intravenous dose, plasma 14C declined with half-lives of 0.3 and 4 hr. After an oral dose, levels of 14C were highest in the liver, kidneys, gastrointestinal tract, and nasal mucosa after 1 and 2 hr. Smaller amounts were present in the heart, lungs, salivary glands, anil bone. Concentrations of 14C were declining after 4 hr, and after 72 hr traces of 14C remained mainly in the kidneys. There were no significant differences in the distribution of 14C between normal rats and those With a skin wound. When applied to the skin of rats, calcium 14C-acexamate was possibly absorbed more rapidly from aqueous solution than from a cream base, and in solution was possibly absorbed slightly more rapidly through a skin wound than through intact skin. About 10% was percutaneously absorbed during 48 hr and 14C was distributed throughout the skin layers. Copyright © 1974 by The American Society for Pharmacology and Experimental Therapeutics