Simultaneous determination of the phase II metabolites of the non steroidal anti-inflammatory drug etodolac in human urine.
Etodolac, an antirheumatic and analgetic drug, is metabolized in humans by hydroxylation and acyl glucuronidation to yield the corresponding 1-O-glucuronides. The acylglucuronides of etodolac and one of its hydroxylated metabolites were determined by HPLC using a RP18 column. In order to increase the lipophilicity of these metabolites the hydroxy groups were acetylated and the carboxylic functions were methylated. In a study with five human volunteers a stereoselective excretion of the acylglucuronides could be observed. The S-etodolac-glucuronide is mainly excreted during the first 6 hours after administration of 400 mg of etodolac whereas the elimination of the R-glucuronide predominates at longer periods of time. The S-glucuronide of 7-hydroxy-etodolac was preferenetively excreted during the period of time observed. An unknown metabolite of etodolac could be characterized by chemical and enzymatically hydrolysis and by MS and NMR.
Berendes
U
U
Institute of Pharmaceutical Chemistry, University of Münster, Germany.
Blaschke
G
G
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism* / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D017308:Etodolac / Q000378:metabolism* / Q000652:urine; D005965:Glucuronates / Q000737:chemistry* / Q000652:urine; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013237:Stereoisomerism; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005965:Glucuronates; D017308:Etodolac