PT  - JOURNAL ARTICLE
AU  - S. J. LAN
AU  - T. J. CHANDO
AU  - A. I. COHEN
AU  - I. WELIKY
AU  - E. C. SCHREIBER
TI  - METABOLISM OF 4-[3-(DIMETHYLAMINO)PROPYL]-3,4-DIHYDRO-2-(1-HYDROXYETHYL)-3-PHENYL-2<em>H</em>-1,4-BENZOTHIAZINE (SQ 11,579) UNDER <em>IN VITRO</em> AND
<em>IN VIVO</em> CONDITIONS BY RATS, DOGS,
AND MONKEY
DP  - 1973 Jul 01
TA  - Drug Metabolism and Disposition
PG  - 619--627
VI  - 1
IP  - 4
4099  - http://dmd.aspetjournals.org/content/1/4/619.short
4100  - http://dmd.aspetjournals.org/content/1/4/619.full
SO  - Drug Metab Dispos1973 Jul 01; 1
AB  - The metabolism of SQ 11,579-14C has been studied both in vitro with rat and dog liver microsomes and in vivo in dogs, rats, and a monkey. Five major metabolites have been isolated from both systems and identified as: 1) monodesmethyl SQ 11,579: 2)N-oxide of SQ 11,579:3) sulfoxide of SQ 11,579: 4) sulfoxide of monodesmethyl SQ 11,579: and 5) an aromatic hydroxylated derivative of SQ 11,579. Quantitative species differences in the formation of metabolites were observed in both systems. In vitro. monodesmethyl SQ 11,579 was the major metabolite formed by rat liver microsomes. Dog liver microsomes formed N-oxide as the major metabolite. In vivo, the glucuronide of SQ 11,579 is the major urinary metabolite in dogs (70-75%) and in the monkey (45%). The major metabolites found in rat urine, however, are monodesmethyl SQ 11,579 (30%) and the sulfoxide of monodesmethyl SQ 11,579 (28%). Incubations were also carried out in the presence of SKF 525-A or Win 13099, reported inhibitors of the hepatic microsomal mixed-function oxidase system. Both compounds inhibited N-demethylation, sulfoxidation, and aromatic hydroxylation by rat or dog liver microsomes, but had no effect on N-oxidation by microsomes of both species. Copyright © 1973 by The American Society for Pharmacology and Experimental Therapeutics