Etodolac metabolism

Indomethacin (Indocin) is an acetic acid derivative related functionally to sulindac (Clinoril), a prodrug with a long half-life, and etodolac (Lodine). They are metabolized in the liver and excreted as metabolites in the... 

Peak plasma concentrations are reached within 2 h. Etodolac shows 99 % binding to plasma protein and an elimination half-life of about 7 h (Brooks and Jamali, 1994). Etodolac is metabolized almost completely to the main metabolites 6- or 7-hydroxy-etodolac, acyl-glucuronide, 8-(1 -hydroxyethyl)-etodolac and 4-ureido-etodolac. The metabolites and a small quantity of etodolac are excreted in the urine. A small amount of conjugated etodolac is excreted through the biliary tract. 

Henrotin Y, Bassleer C, Franchimont P. In vitro effects of etodolac and acetylsalicylic acid on human chondrocyte metabolism. Agents Actions. 1992 36 317-323. 

Several metabolites of etodolac have been synthesized to confirm their identity during drug metabolism studies including 6-hydroxyetodolac, N-methyletodolac, 4-ureidoetodolac, 8-(l -hydroxy) etodolac, and 4-oxoetodolac [8],... 

No significant stereoselectivity in etodolac enantiomeric metabolism was noted in a 24 hour urine recovery study [40]. Analytical methods for the... 

Etodolac is rapidly and well absorbed orally. It is highly bound to plasma protein and undergoes hepatic metabolism and renal excretion. The drug may undergo enterohepatic circulation in humans its half-life in plasma is about 7 hours. 

Becker-Scharfenkamp, U. Blaschke, G. Evaluation of the stereoselective metabolism of the chiral analgesic drug etodolac by high-performance liquid chromatography. J.Chromatogr., 1993, 621, 199-207... 

As a class, the chiral NSAiDs display a wide range of stereoselectivity in plasma concentrations in humans (Table 1, Fig. 7). This is mostly due to variations in metabolic clearances of the enantiomers. Flurbiprofen and ketoprofen possess S R AUC ratios of close to one (Table 1) [246,247]. In contrast, drugs such as fenoprofen, etodolac, and ketorolac possess S R ratios that differ substantially from unity (Table 1) [248-250]. In all cases, concentrations of NSAID eutomer exceed those of distomer. Etodolac and ketorolac provide notable exceptions to this commonality, in that concentrations of distomer are much higher than those of the eutomer. 

Brocks, D.R. Jamah, F. Enantioselective pharmacokinetics of etodolac in the rat tissue distribution, tissue binding, and in vitro metabolism. J. Pharm. Sci. 1991, 80, 1058 1061. 

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