Studies on the metabolism of diltiazem in man.
The human urinary metabolites of diltiazem were analyzed by thin-layer chromatography (TLC) and gas chromatography-mass spectrometry. Diltiazem was metabolized by deacetylation, N-demethylation, O-demethylation and conjugation. Metabolite MA, N- monodemethyl -diltiazem, was identified as a new major metabolite in human urine, and four metabolites were identified as deacetyl-diltiazem (M1), deacetyl-N- monodemethyl -diltiazem (M2), deacetyl-O-demethyl-diltiazem (M4), deacetyl-N,O-demethyl-diltiazem (M6) which were known as rat urinary metabolites. Metabolite M2, M4 and M6 were converted in part to glucuronides and/or sulfates. Unchanged diltiazem and metabolite MA were determined in human plasma and urine by TLC-densitometry. Diltiazem and metabolite MA excreted in 24-h urine were 44.4 and 48.5% of the total unconjugated form, respectively. The mean plasma level of metabolite MA was approximately one-third of diltiazem level. On the basis of these findings, a probable metabolic pathway of diltiazem in man is presented.
D000328:Adult; D000818:Animals; D001552:Benzazepines / Q000378:metabolism*; D001711:Biotransformation; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002855:Chromatography, Thin Layer; D004110:Diltiazem / Q000097:blood / Q000378:metabolism* / Q000652:urine; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity
D001552:Benzazepines; D004110:Diltiazem