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Etodolac

A Preliminary Review of its Pharmacodynamic Activity and Therapeutic Use

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Summary

Synopsis: Etodolac1 is a new non-steroidal agent (NSAID) with anti-inflammatory and analgesic activity. It has been studied in rheumatoid arthritis, osteoarthritis, and pain resulting from minor surgery. In the latter setting, etodolac is at least as effective as aspirin in terms of overall pain relief, and the duration of analgesic effect of a dose of 200 to 400mg is longer than that of aspirin. In rheumatoid arthritis, etodolac, administered twice daily, appears comparable in efficacy to moderate doses of aspirin (3 to 4g daily), but is better tolerated. To date, etodolac has not been compared clinically with analgesics other than aspirin and sulindac. As with other non-steroidal agents, gastrointestinal complaints are the most frequently reported side effects, but the incidence of most gastrointestinal effects was only slightly higher than with placebo. Thus, from studies in small numbers of patients etodolac appears at least as effective as aspirin and better tolerated. The relatively low incidence of gastrointestinal side effects in these studies awaits confirmation in well designed comparisons with widely used NSAIDs.

Pharmacodynamic Studies: Etodolac is a non-steroidal anti-inflammatory drug (NSAID) with analgesic activity. Like other NSAIDs, etodolac is an inhibitor of prostaglandin synthesis at the cyclo-oxygenase level. The analgesic effect of full doses of etodolac is longer than that of aspirin, lasting up to 8 hours. In rats, etodolac had a more favourable ratio of anti-inflammatory activity to gastric irritant propensity than other studied NSAIDs and parallel group studies in healthy subjects and arthritic patients have indicated that usual therapeutic doses of etodolac cause less faecal blood loss than aspirin and several other NSAIDs.

Pharmacokinetic Properties: After oral administration, peak serum concentrations of 16 and 25 mg/L are attained within 2 hours of administering 200 and 400mg, respectively. Etodolac is highly bound to plasma proteins and has an estimated volume of distribution of 0.4 L/kg. Etodolac is excreted primarily in the urine, and 60% of a dose is recovered within 24 hours. Greater than 60% of the metabolites are hydroxylated with glucuronic conjugation. The half-life of etodolac is approximately 7 hours in healthy subjects.

Therapeutic Trials: Etodolac has been studied in rheumatoid arthritis, osteoarthritis, and pain resulting from minor surgical procedures. In usually small numbers of patients with rheumatoid arthritis, etodolac has been shown to be superior to placebo on the basis of objective and subjective criteria. When compared with other NSAIDs, etodolac 300 and 400mg daily has tended to be more effective than aspirin 3 to 4g daily and was similar in efficacy to sulindac 400mg daily. In postsurgical pain, etodolac 100 to 200mg was approximately equivalent to aspirin 650mg in providing pain relief, although etodolac had a longer duration of action.

Side Effects: At dosages used in the treatment of rheumatoid arthritis, etodolac has generally been well tolerated. Gastrointestinal complaints have been the most frequent, although usually only more frequent than during placebo therapy, with headaches and dizziness being relatively rare. Under the conditions existing in controlled therapeutic trials, etodolac has been better tolerated than therapeutically equivalent doses of aspirin. Further studies are required to determine the relative incidence of side effects of etodolac in comparison with other NSAIDs.

Dosage: The usual dose of etodolac in arthritic conditions is 200mg twice daily. For acute pain, the recommended dose is 200mg every 6 to 12 hours as needed.

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Author information

Authors and Affiliations

  1. Atlanta VA Medical Center, Atlanta, USA

    Sharon Lynch & Rex N. Brogden

  2. ADIS Drug Information Services, Centorian Drive, Private Bag, Mairangi Bay, Auckland 10, New Zealand

    Sharon Lynch & Rex N. Brogden

Authors
  1. Sharon Lynch
  2. Rex N. Brogden

Additional information

Various sections of the manuscript have been reviewed by:H. Berry, Department of Rheumatology and Rehabilitation, King’s College Hospital, London, England;G.W. Gaston, University of Maryland, Baltimore College of Dental Surgery, Baltimore, Maryland, USA;G.V. Gordon, Lankenau Medical Building, Lancaster Avenue West of City Line, Philadelphia, Pennsylvania, USA;F.D. Hart, Harley Street, London, England;A. Hedges, Department of Clinical Pharmacology, St Bartholomew's Hospital Medical College, London, England;E.C. Huskisson, Department of Rheumatology, St Bartholomew's Hospital Medical College, London, England;S.H. Roth, Arthritis Center Ltd., St Luke's Hospital, Phoenix, Arizona, USA;J.C. Steigerwald, Division of Rheumatology, University of Colorado Health Sciences Center, Denver, Colorado, USA;M. Thompson, Yarru House, Gosforth, Newcastle upon Tyne, United Kingdom.

‘Ultradol’ (Ayerst Laboratories, USA); Lodine (Ayerst Laboratories, UK); Ramodar (Wyeth Laboratories, UK).

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