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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.
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- Abe S, Moriizumi T, Ohsima T, Higuchi S, Otomo S, et al. Studies on toxicity of oxaprozin (5) tolerance and physical dependence liability in rats. Pharmacometrics 27: 345–352, 1984Google Scholar
- Bono RF, Finkel S, Goodman HF, Hanna CB, Rabinowitz SR, et al. Multicenter, double-blind comparison of oxaprozin, phenylbutazone, and placebo therapy in patients with tendinitis and bursitis. Clinical Therapeutics 6: 79–85, 1983Google Scholar
- Carlson RP, Chang J, Lewis AJ, Gilman SC. Immunopharmacological properties of oxaprozin (Oxapro®; 4,5-diphenyl-2-oxazolepropionic acid). Abstract no. 3412. Federation Proceedings 42: 875, 1983Google Scholar
- Editorial. Duraprox (oxaprozin) Wyeth. In World Pharmaceutical Introductions, pp. PR.28–PR.30, IMS World Publications, London, 1983Google Scholar
- Fawthrop FW, Mellor D, Highton J, Palmer DG. Experimental synergism between oxaprozin and diflunisal. Proceedings of the University of Otago Medical School 63: 15, 1985Google Scholar
- Ferreira SH, Moncada S, Vane JR. Prostaglandins and signs and symptoms of inflammation. In Robinson & Vane (Eds) Prostaglandin synthetase inhibitors, pp. 175–187, Raven Press, New York, 1974Google Scholar
- Goldfarb S, Walker BR, Agus ZS. Uricosuric and hypouricemic effects of oxaprozin — a non-steroidal anti-inflammatory agent. Abstract. Kidney International 25: 300, 1984Google Scholar
- Greenberg A, Mitnick PD, DeOreo P, Weiner B, Walker B, et al. Differing renal effects of two non-steroidal anti-inflammatory agents (NSAID) in man. Abstract. Clinical Research 28: 237A, 1980Google Scholar
- Hubsher JA, Walker BR. Oxaprozin once daily and ibuprofen qid in the treatment of rheumatoid arthritis: a multicenter study. Abstract no. A45. Clinical Pharmacology and Therapeutics 33: 267, 1983Google Scholar
- Hubsher JA, Bono RF, Finkel S, Goodman HF, Hanna CB, et al. Comparison of the efficacy and safety of oxaprozin (4,5-diphenyl-2-oxazole propionic acid) and phenylbutazone versus placebo in the treatment of patients with acute tendinitis/bursitis. Abstract. Clinical Research 30: 806A, 1982aGoogle Scholar
- Hubsher JA, Walker BR, Caldwell JR. Oxaprozin (WY-21,743) once daily and aspirin q.i.d. in the treatment of osteoarthritis: a multicentre study. Abstract. Clinical Research 31: 629A, 1983Google Scholar
- Janssen FW, Chiang ST, Walker BR, Ruelius HW. Disposition of oxaprozin in healthy subjects and certain disease states. Current Therapeutic Research 35: 363–376, 1984Google Scholar
- Lasseter KC, Chiang ST, Rogers SL, Walker BR. Pharmacokinetics of oxaprozin in patients with hepatic impairment. Abstract. Clinical Research 33: 284A, 1985Google Scholar
- Lewis AJ, Carlson RP, Chang J, Gilman SC, Nielsen S, et al. The pharmacological profile of oxaprozin, an antiinflammatory and analgesic agent with low gastrointestinal toxicity. Current Therapeutic Research 34: 777–794, 1983Google Scholar
- Lewis AJ, Janssen FW, Bonney SL, Ruelius HW, Hubsher JA, et al. Oxaprozin. In Anti-rheumatic and Anti-inflammatory Drugs, Vol. II, CRC Press, 1986Google Scholar
- Lopes Vaz A. Ensaio comparativo duplamente cega com oxa prozin vs indometacina ≪ retard ≫ na artrite reumatóide. Rheumatologia Multidisciplinar (Suppl): 46–52, 1983Google Scholar
- Morrison G, DiPonzio M, Rogers SL, Audet P, Walker BR. The steady-state pharmacokinetics of oxaprozin in patients undergoing hemodialysis. Abstract. Clinical Research 33: 286A, 1985Google Scholar
- Pediatric Rheumatology Collaborative Study Group. A once-daily antiinflammatory drug, oxaprozin, in the treatment of juvenile rheumatoid arthritis. Journal of Rheumatology 12: 384–386, 1985Google Scholar
- Powell WR, Bonney SL, Hubsher JA, Walker BR. Oxaprozin (O) and Piroxicam (P) once daily in the treatment of osteoarthritis. Abstract no. C26. Clinical Pharmacology and Therapeutics 37: 222, 1985Google Scholar
- Rainsford KD. Comparison of the gastric ulcerogenic activity of new non-steroid anti-inflammatory drugs in stressed rats. British Journal Pharmacology 73: 226P–227P, 1981Google Scholar
- Scavone JM, Greenblatt DJ, Matlis R, Harmatz JS. Interaction of oxaprozin with acetaminophen, Cimetidine, and ranitidine. Abstract. Journal of Clinical Pharmacology 25: 461, 1985Google Scholar
- Suwa T, Kohno Y, Urano H, Miragawa T, Kyogoku K. Metabolic fate of oxaprozin (2) distribution of 14C-oxaprozin. Pharmacometrics 27: 141–146, 1984aGoogle Scholar
- Suwa T, Urano H, Kohno Y, Minagawa T, Kyogoku K. Metabolic fate of oxaprozin (4) foeto-placental transfer, excretion into milk and repeated administration of 14C-oxaprozin in rats. Pharmacometrics 27: 157–163, 1984bGoogle Scholar
- Tsuchida K, Higuchi S, Kurachi M, Arai I, Isobe Y, et al. General pharmacology of oxaprozin (2) effects on the cardiovascular and autonomic nervous systems. Pharmacometrics 27: 329–344, 1984Google Scholar
- Vane JR. Mode of action of aspirin and similar compounds. In Robinson & Vane (Eds) Prostaglandin synthetase inhibitors, pp. 155–163, Raven Press, New York, 1974Google Scholar
- Verburg-Ochs B, Ochs HR, Greenblatt DJ. Oxaprozin kinetics in congestive heart failure. Clinical Pharmacology and Therapeutics 37: 235, 1985Google Scholar
- Walker B, Bonney SL. Perfil terapêutico do oxaprozin. Rheumatologia Multidisciplinar (Suppl.): 75–78, 1983Google Scholar