Metabolic fate of delmopinol in man after mouth rinsing and after oral administration.
1. The metabolism of delmopinol, an inhibitor of plaque formation and gingivitis. has been studied after mouth rinsing or an oral dose of 14C-delmopinol to healthy male volunteers. The metabolite pattern was studied in urine and plasma samples (unhydrolysed or hydrolysed with conjugate cleaving enzymes) by liquid chromatography (LC) with radio detection. Metabolite identifications were carried out by gas chromatography-electron-impact mass spectrometry (GC-MS) and by liquid chromatography-thermospray mass spectrometry (LC-MS). 2. The metabolic clearance of delmopinol was high, and < 0.2% of the dose was excreted as intact delmopinol in the urine. The main metabolites were, for both administration routes, glucuronide conjugates of delmopinol and of (omega-1-hydroxy) delmopinol. These metabolites were predominant and accounted for nearly the entire urinary radioactivity and most of the plasma radioactivity. After mouth rinsing, parent delmopinol was also one of the main compounds in plasma. 3. Several other products of oxidation of the aliphatic side-chain were present in minor amounts in urine. These metabolites also appeared to be excreted as glucuronic acid conjugates. 4. Glucuronidated (omega-1-hydroxy) delmopinol separated into three peaks by the LC system used. This could be due to different chromatographic properties of conjugate isomers, positional or optical.
Eriksson
B
B
Pharmacokinetics and Metabolism, Active Biotech Research AB, Lund, Sweden. birgitta.eriksson@activebiotech.com
Hallström
G
G
Ottersgård Brorsson
A K
AK
Svensson
L
L
Gunnarsson
P O
PO
D002250:Carbon Radioisotopes; D002853:Chromatography, Liquid; D008401:Gas Chromatography-Mass Spectrometry; D020719:Glucuronides / Q000097:blood / Q000652:urine; D006801:Humans; D008297:Male; D015394:Molecular Structure; D009025:Morpholines / Q000493:pharmacokinetics*; D009067:Mouthwashes / Q000493:pharmacokinetics*; D013501:Surface-Active Agents / Q000493:pharmacokinetics
D002250:Carbon Radioisotopes; D020719:Glucuronides; D009025:Morpholines; D009067:Mouthwashes; D013501:Surface-Active Agents; C073738:delmopinol