Metabolism of doxylamine succinate in Fischer 344 rats. Part III: Conjugated urinary and fecal metabolites.
Elimination and metabolic profiles of the glucuronide products of doxylamine and its N-demethylated metabolites were determined after the oral administration of (14C)-doxylamine succinate (13.3 and 133 mg/kg doses) to male and female Fischer 344 rats. The cumulative urinary and fecal eliminations of these conjugated doxylamine metabolites at the 13.3 mg/kg dose were 44.4 +/- 4.2% and 47.3 +/- 8.1% of the total recovered dose for male and female rats, respectively. The cumulative urinary and fecal eliminations of conjugated doxylamine metabolites at the 133 mg/kg dose were 55.2 +/- 2.6% and 47.9 +/- 2.5% of the total recovered dose for male and female rats, respectively. The conjugated doxylamine metabolites that were isolated, quantitated, and identified are doxylamine O-glucuronide, N-desmethyl-doxylamine O-glucuronide, and N,N-didesmethyldoxylamine O-glucuronide.
Holder
C L
CL
Food and Drug Administration, National Center for Toxicological Research, Jefferson, Arkansas 72079.
Siitonen
P H
PH
Slikker
W
W
Branscomb
C J
CJ
Korfmacher
W A
WA
Thompson
H C
HC
Cerniglia
C E
CE
Gosnell
A B
AB
Lay
J O
JO
D000284:Administration, Oral; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004319:Doxylamine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism* / Q000652:urine; D005243:Feces / Q000032:analysis*; D005260:Female; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000378:metabolism* / Q000652:urine; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D015394:Molecular Structure; D011725:Pyridines / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D012737:Sex Factors
D006634:Histamine H1 Antagonists; D011725:Pyridines; D004319:Doxylamine; C035385:doxylamine succinate