Drug Evaluation

Drugs

, Volume 32, Issue 4, pp 291-312

First online:

Oxaprozin

A Preliminary Review of Its Pharmacodynamic and Pharmacokinetic Properties, and Therapeutic Efficacy
  • Peter A. ToddAffiliated withADIS Drug Information Services
  • , Rex N. BrogdenAffiliated withADIS Drug Information Services

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Summary

Synopsis: Oxaprozin1 is a newer non-steroidal anti-inflammatory drug advocated for use in painful rheumatic and inflammatory, conditions. As is the case with some other newer non-steroidal anti-inflammatory drugs, oxaprozin offers the convenience of once-daily administration. Published data suggest that oxaprozin 1200mg once daily is comparable in effectiveness with usual dosages of aspirin, ibuprofen, indomethacin, naproxen, piroxicam and sulindac in the treatment of rheumatoid arthritis and osteoarthritis. More controlled clinical trials in adequate numbers of patients are necessary to evaluate its potential in other rheumatic and inflammatory conditions. Oxaprozin produced fewer gastrointestinal side effects than aspirin, and the short term tolerability of oxaprozin was similar to that of other non-steroidal anti-inflammatory drugs. If further definition of its efficacy and tolerability compared with other non-steroidal anti-inflammatory drugs during long term therapy confirms these initially favourable results, then oxaprozin would appear to offer a useful and convenient alternative in the treatment of painful rheumatic and inflammatory conditions.

Pharmacodynamic Properties: In vitro studies show that oxaprozin, in common with aspirin and other non-steroidal anti-inflammatory drugs, is a potent inhibitor of the cyclo-oxygenase pathway of prostaglandin synthesis. In standard animal models of anti-inflammatory, analgesic and antipyretic activity, oxaprozin is similar in potency to aspirin but less potent than naproxen, piroxicam and indomethacin. Oxaprozin is mildly uricosuric.

The ulcerogenic activity of oxaprozin in animals is less than other standard reference agents such as aspirin, ibuprofen and naproxen when equivalent anti-inflammatory dosages are compared. Unlike most other non-steroidal anti-inflammatory drugs which produce lesions in both the stomach and small intestine of animals, oxaprozin only produces gastric lesions. In man, oxaprozin 1200mg daily produces less faecal blood loss and gastric irritation than aspirin 3900mg daily.

In common with other non-steroidal anti-inflammatory drugs, oxaprozin is a potent inhibitor of platelet aggregation and prolongs bleeding time in man.

In healthy subjects, renal plasma flow is unaffected by the administration of oxaprozin 1200mg daily for 1 week.

Pharmacokinetic Properties: The kinetics of oxaprozin after single or repeated oral administration are characterised by extensive protein binding (⩾ 99.5%), limited volume of distribution (0.15 to 0.25 L/kg), and low rate of systemic clearance (0.0017 to 0.0031 L/h/kg). This leads to a long elimination half-life (about 50 to 60 hours), which makes the drug suitable for once daily administration.

Following single oral doses of oxaprozin 300 to 1200mg, absorption appears complete, although bioavailability studies comparing oral and intravenous administration have not been reported. Peak plasma concentrations are reached in about 2 to 6 hours in most subjects, and absorption is unaffected by food. The plasma concentration of total oxaprozin is non-linearly related to dose, but that of unbound oxaprozin is linearly related. Steady-state plasma concentrations are reached after 4 to 7 days following the repeated oral administration of oxaprozin 600 or 1200mg once daily, when little fluctuation between maximum and minimum plasma concentrations occurs.

There are 2 primary metabolic pathways of oxaprozin excretion in man. Oxaprozin glucuronide is excreted in urine, and 2 hydroxylated metabolites of oxaprozin are excreted mainly as glucuronides in urine and bile. Hydroxylated metabolite excretion is evenly divided between urine and bile. About two-thirds of a radiolabelled dose of oxaprozin is recovered in urine and one-third in faeces.

The sex or age of subjects, and the condition of rheumatoid arthritis, appear to have little influence on the overall disposition of oxaprozin. In patients with renal impairment, plasma concentrations of unbound oxaprozin are increased compared with healthy subjects after a single oral dose of oxaprozin. Further study is required with repeated doses to formulate dosage recommendations. However, an initial dosage not exceeding 600mg once daily has been recommended in azotaemic patients. The free fraction of oxaprozin in plasma is also significantly increased in patients with hepatic impairment or congestive heart failure.

Therapeutic Trials: Most of the studies comparing oxaprozin with other non-steroidal anti-inflammatory drugs in patients with rheumatoid arthritis and osteoarthritis have been of a relatively short duration (4 to 24 weeks). However, from these preliminary data it appears that oxaprozin 1200mg once daily is as effective as aspirin 650 to 812mg 4 times daily in osteoarthritis and as effective as aspirin 925mg 4 times daily in rheumatoid arthritis, with statistically significant results in favour of oxaprozin for some clinical assessments. Oxaprozin was generally better tolerated than aspirin. The efficacy and tolerability of oxaprozin 1200mg once daily were similar to those of naproxen 250mg 3 times daily and piroxicam 20mg once daily in patients with osteoarthritis, and similar to those of ibuprofen 300 to 400mg 4 times daily, sustained release indomethacin 75mg twice daily, naproxen 250mg twice daily and sulindac 200mg twice daily in patients with rheumatoid arthritis.

Single and/or brief reports indicate that oxaprozin may be effective in other rheumatic, inflammatory and painful conditions, such as gouty arthritis, ankylosing spondylitis, juvenile rheumatoid arthritis, tendinitis, bursitis and Behçet’s disease. On the basis of one study in patients with postsurgical dental pain, it appears that the analgesic potency of single oral doses of oxaprozin 1200mg and aspirin 650mg are similar but that oxaprozin has a longer duration of action.

Further studies involving greater numbers of patients and extending over longer periods are needed to judge more accurately the relative efficacy and tolerability of oxaprozin compared with commonly used non-steroidal anti-inflammatory drugs in rheumatic and other painful or inflammatory conditions.

Side Effects: Oxaprozin has been well tolerated in most patients to date, and few severe adverse effects have been reported. However, further data are required to determine clearly its side effect profile during longer term therapy, particularly when compared with other frequently used non-steroidal anti-inflammatory drugs. The most frequently reported side effects have been mild gastrointestinal complaints, followed by mild central nervous system effects and rash. A phototoxic reaction has been observed in patients with juvenile rheumatoid arthritis.

From comparative data which are available, oxaprozin appears better tolerated than equivalent dosages of aspirin, in that it causes fewer complaints of gastrointestinal effects and tinnitus. The frequency, severity and nature of side effects appear similar with oxaprozin and usual therapeutic dosages of ibuprofen, naproxen, piroxicam and sulindac.

Dosage: The starting and maintenance dosage of oral oxaprozin is 1200mg once daily, although a starting dosage of 600mg once daily is recommended in azotaemic patients.