Etodolac dosing

Taha, A. S., McLaughlin, S., Holland, P. J., Kelly, R. W., Sturrock, R. D., Russel, R. I. Effect of repeated therapeutic doses of naproxen and etodolac on gastric and duodenal mucosal prostaglandins (PGs) in rheumathoid arthritis (RA) Gut 1989, 30, A751. 

Etodolac achieves a Cmax of 15 to 20 pg/mL following a 200-mg oral dose... 

Etodolac distributes well into synovial fluid, the proposed primary site of action of NSAID s. Following multiple doses of 200 mg twice daily for 7 days, the Cmax in synovial fluid was 2.6 pg /mL and the tmax was 3.2 hours [44]. The synovial fluid AUC of total etodolac was about 67% of the serum values [44]. The AUC of the unbound etodolac was 172% of the serum values. After a single 200 mg dose of etodolac, the ratio of (S)-etodolac to (i )-etodolac in six subjects with rheumatoid arthritis was 0.074 in plasma and 0.17 in synovial fluid [45]. 

In serum, 90% of radiolabeled drug was found as unconjugated etodolac, of which 70% to 80% was present as unchanged etodolac, 10% as 7-hydrocy-etodolac, and 1% to 2% as 6-hydeoxy-etodolac [15], In urine, less than 5% of the dose is unconjugated etodolac, and 20% is the conjugated etodolac glucuronide. The hydroxy metabolites (6-, 7-, 8-(hydroxyethyl)-) of etodolac together account for about 46% of the dose [15]. The 4-ureido- metabolite accounts for 8% of the dose in urine. 

Etodolac shows a terminal elimination half-life of 6 to 8 hours following administration of capsules, tablets, sustained-release formulation, and suppositories [38]. The elimination of etodolac is not dose dependent. 

The AUC increases in a dose dependent manner for 200 to 1600 mg single doses [21], Individual enantiomers show similar half-lives [40]. Following radiolabeled etodolac administration, 69% to 76% of the dose was recovered in urine over 7 days. Urine and feces together accounted for 80% to 92% of dose [15]. Biliary excretion is a minor route for the elimination of etodolac [40]. 

Jacob G, Messina M, Ketmedy J, Epstein C, Sanda M, Mullane J. Mittimum effective dose of etodolac for the treatment of rherrmatoid arthritis. J Chn Pharmacol... 

Etodolac is another acetic acid derivative with some degree of COX-2 selectivity. Thus, at antiinflammatory doses, the frequency of gastric irritation may be less than with other tNSAIDs. 

A single oral dose (200 to 400 mg) of etodolac (Lodine) provides postoperative analgesia that typically lasts for 6 to 8 hours. Etodolac also is effective in the treatment of osteoarthritis and rheumatoid arthritis, and the drug appears to be uricosuric. A sustained-release preparation (Lodine XL) is available, allowing once-a-day administration. 

In a pharmacological study, etodolac did not interact significantly with warfarin, suggesting dose adjustments are unlikely to be needed. Note that all NSAIDs increase the risk of gastrointestinal bleeding, and an increased risk is seen when they are combined with anticoagulants. 

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