RT Journal Article
SR Electronic
T1 Metabolism of kadsurenone and 9,10-dihydrokadsurenone in rhesus monkeys and rat liver microsomes.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 737
OP 743
VO 16
IS 5
A1 K L Thompson
A1 M N Chang
A1 J C Chabala
A1 S H Chiu
A1 D Eline
A1 H B Hucker
A1 B M Sweeney
A1 S D White
A1 B H Arison
A1 J L Smith
YR 1988
UL http://dmd.aspetjournals.org/content/16/5/737.abstract
AB The metabolism of the PAF antagonists kadsurenone and tritium-labeled 9,10-dihydrokadsurenone was studied in rhesus monkeys and rat liver microsomes. The monkey metabolites of the two drugs were isolated as their glucuronide conjugates from the urine of iv dosed males. The metabolites from both monkey and microsomal metabolism were purified by reverse phase HPLC and identified by spectral (NMR, UV, and mass spectrometric) analysis. The principal pathway of biotransformation of the tritium-labeled 9,10-dihydrokadsurenone in monkeys was hydroxylation of the C-5 propyl side chain to give two metabolites, 10-hydroxy-9,10-dihydrokadsurenone and 9-hydroxy-9,10-dihydrokadsurenone. These compounds were excreted as glucuronides. Microsomal incubation of tritium-labeled 9,10-dihydrokadsurenone yielded the 10-, 9-, and 8-hydroxy-9,10-dihydrokadsurenone as major metabolites. Kadsurenone was also metabolized at the C-5 side chain, an allyl group. The monoglucuronide of 9,10-dihydroxykadsurenone was isolated from monkey urine. Spectral analysis was not definitive as to the site of conjugation, and the structure of the metabolite was assigned as the C-10 conjugate. A major metabolite of rat liver microsomal incubation of kadsurenone was 9,10-dihydroxykadsurenone.