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Journal of Pharmaceutical and... May 2000A reversed phase linear gradient liquid chromatographic method was developed for the separation and quantitative determination of the seven known process related...
A reversed phase linear gradient liquid chromatographic method was developed for the separation and quantitative determination of the seven known process related impurities and one degraded product of oxaprozin in the bulk drug material. An Inertsil-ODS 3V (150 x 4.6 mm), 5 microm column was operated with a phosphate buffer acetonitrile gradient. Detection was carried out on a UV detector at 254 nm. This method has been proved to be accurate and sensitive. The limits of detection (LOD) and limits of quantification (LOQ) of impurities were in the order of 5-60 ng and 16-200 ng, respectively. In addition to its ruggedness and robustness, this method offers identification of all eight impurities in a single run.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Chromatography, Liquid; Drug Contamination; Oxaprozin; Propionates; Quality Control; Reproducibility of Results
PubMed: 10768354
DOI: 10.1016/s0731-7085(99)00305-2 -
Journal of the American Pharmaceutical... 2000
Topics: Anti-Inflammatory Agents, Non-Steroidal; Drug Industry; Oxaprozin; Pharmaceutical Preparations; Pharmacists; Propionates; Tablets
PubMed: 10665255
DOI: 10.1016/s1086-5802(16)31041-5 -
Current Medical Research and Opinion 1999Although progress has been made in the clinical metrology of pain in rheumatoid arthritis, much further work remains. The preferred methods of measurement remain... (Comparative Study)
Comparative Study
Although progress has been made in the clinical metrology of pain in rheumatoid arthritis, much further work remains. The preferred methods of measurement remain debatable. In this longitudinal, open study, a comparison of eight self-rating pain scales has been conducted. A total of 124 patients entered the four-week study after completing a 3-7-day NSAID-free washout period. Patients were assigned to treatment with oxaprozin 1200 mg p.o. once daily with titration permitted between 600 mg and 1800 mg. Rescue analgesia with acetaminophen (paracetamol) 325 mg (maximum 2600 mg) was permitted. At the end of the washout and treatment period, patients completed eight self-administered pain rating scales. All pain measures detected clinically important and statistically significant improvements in pain. The pain scales differed in their degree of responsiveness. The Likert and visual analogue scales and their primary variations (continuous chromatic analogue and numerical scales) were more responsive than more complex measures. A positive correlation between initial pain rating and subsequent pain response was confirmed in this study. We conclude that, while pain is a subjective sensory phenomenon, its perceived severity can be evaluated using a variety of self-administered pain scales, all of which are capable of detecting improvements in health status following effective pharmacological intervention.
Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Evaluation Studies as Topic; Female; Humans; Longitudinal Studies; Male; Middle Aged; Oxaprozin; Pain Measurement; Propionates; Surveys and Questionnaires
PubMed: 10494495
DOI: 10.1185/03007999909113372 -
Current Medical Research and Opinion 1999Although progress has been made in the clinical metrology of pain in osteoarthritis, much further work remains. The preferred methods of measurement remain debatable. In... (Comparative Study)
Comparative Study
Although progress has been made in the clinical metrology of pain in osteoarthritis, much further work remains. The preferred methods of measurement remain debatable. In this longitudinal, open study, a comparison of eight self-rating pain scales has been conducted. A total of 333 patients entered the four-week study after completing a 3-7 day NSAID-free washout period. Patients were assigned to treatment with oxaprozin 1200 mg p.o. once daily with titration permitted between 600 mg and 1800 mg. Rescue analgesia with acetaminophen (paracetamol) 325 mg (maximum 2600 mg) was allowed. At the end of the washout and the treatment period, patients completed eight self-administered pain scales. All pain measures detected clinically important and statistically significant improvements in pain. The pain scales differed in their degree of responsiveness. The Likert and visual analogue scales and their primary variations (continuous chromatic analogue and numerical scales) were more responsive than more complex measures. A positive correlation between initial pain rating and subsequent pain relief was confirmed in this study. We conclude that, while pain is a subjective sensory phenomenon, its perceived severity can be evaluated using a variety of self-administered pain scales, all of which are capable of detecting improvements in health status following effective pharmacological intervention.
Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Chronic Disease; Evaluation Studies as Topic; Female; Humans; Longitudinal Studies; Male; Middle Aged; Osteoarthritis; Oxaprozin; Pain Measurement; Propionates; Surveys and Questionnaires
PubMed: 10494494
DOI: 10.1185/03007999909113371 -
The Annals of Pharmacotherapy Sep 1999To describe a case of symptomatic hepatotoxicity attributed to oxaprozin use.
OBJECTIVE
To describe a case of symptomatic hepatotoxicity attributed to oxaprozin use.
CASE SUMMARY
A 41-year-old white woman was admitted to the hospital with malaise, anorexia, and right upper quadrant pain. The patient was found to have severe jaundice with liver enzyme elevation. Laboratory test results for potential etiologies were negative, except for the use of oxaprozin for the preceding six weeks. Diagnosis of drug-induced hepatotoxicity was made by liver biopsy. The patient's symptoms resolved and liver enzymes normalized after oxaprozin was discontinued.
DISCUSSION
Symptomatic hepatic effects attributable to most nonsteroidal antiinflammatory drugs (NSAIDs) are rare and usually mild. Oxaprozin has been shown to cause mild elevation of liver enzymes in clinical studies. This is the second reported case of presumed oxaprozin-induced icteric hepatitis. The mechanism of oxaprozin-induced hepatotoxicity is unclear, but is thought to be due to metabolic idiosyncrasy. Most NSAID reactions are hepatocellular and occur because of individual susceptibility (idiosyncrasy). In general, people aged >40 years and women are more predisposed to NSAID-induced liver injury.
CONCLUSIONS
Although this toxicity is rare, clinicians should be aware of the potential for oxaprozin to cause hepatotoxicity and use caution when prescribing this medication. This case also stresses the importance of careful inquiry regarding drug or toxin exposure in cases of unexplained hepatitis.
Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Biopsy; Chemical and Drug Induced Liver Injury; Female; Humans; Liver; Liver Diseases; Oxaprozin; Propionates; Shoulder Pain
PubMed: 10492496
DOI: 10.1345/aph.18408 -
Journal of Analytical Toxicology 1999A method for the extraction of oxaprozin from equine urine and serum and its quantitation by high-performance liquid chromatography-ultraviolet detection is presented....
A method for the extraction of oxaprozin from equine urine and serum and its quantitation by high-performance liquid chromatography-ultraviolet detection is presented. Confirmation of oxaprozin in postadministration extracts was accomplished by gas chromatographic- mass spectrometric analysis of methylated extracts or liquid chromatography with tandem mass spectrometry daughter ion mass spectra of underivatized extracts. Daypro, a formulation of oxaprozin, was administered orally at a dose of 4.8 g to four standardbred mares. Urine and serum samples were collected to 120 h postadministration. Base hydrolysis of equine urine before extraction resulted in an increase in the amount of oxaprozin measured, an indication of conjugation by ester formation. The urinary elimination profiles of each horse were significantly different from each other with more than one peak in oxaprozin concentration before the 29-31-h collection time. After this collection time, the differences between the oxaprozin urinary concentrations of each horse follow each other more closely. The peak average urinary concentrations of oxaprozin were 25.1 and 17.0 microg/mL at collection times of 8-10 and 18-22 h, respectively. The latest detection of oxaprozin in urine was at the last collection time of 119-121 h postadministration at a concentration close to the detection limit of approximately 0.1 microg/mL. The serum elimination profiles do not vary between horses as much as the urinary elimination profiles. The peak average serum concentration was 49.0 microg/mL at a collection time of 6 h postadministration. The latest detection was at the last collection time of 120 h. Oxaprozin is metabolized in the horse by hydroxylation. Two major urinary metabolites were isolated and identified as hydroxylated oxaprozin. The two urinary metabolites were isolated from equine postadministration urine and analyzed by mass spectrometry and proton nuclear magnetic resonance spectroscopy, which showed that the hydroxylation had occurred at the para positions of the two aromatic rings.
Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Female; Horses; Hydroxylation; Oxaprozin; Propionates; Ultraviolet Rays
PubMed: 10445486
DOI: 10.1093/jat/23.4.242 -
Journal of Cutaneous Medicine and... Jan 1999Pseudoporphyria is a photosensitive bullous skin disease that is distinguished from porphyria cutanea tarda (PCT) by its normal porphyrin profile. Drugs are a major... (Review)
Review
BACKGROUND
Pseudoporphyria is a photosensitive bullous skin disease that is distinguished from porphyria cutanea tarda (PCT) by its normal porphyrin profile. Drugs are a major cause of this disease, and the list of culprits is continually expanding. Nonsteroidal antiinflammatory agents (NSAIDs), especially naproxen and other propionic acid derivatives, appear to be the most common offenders.
OBJECTIVE
The study was carried out to increase awareness about the etiology and characteristic features of pseudoporphyria.
METHODS
We report two cases of pseudoporphyria caused by naproxen and oxaprozin. We review the current English language literature on this entity and discuss its clinical features, histology, ultrastructure, etiology, and pathophysiology.
RESULTS
A 44-year-old man taking naproxen for chronic low back pain and a 20-year-old woman on oxaprozin for rheumatoid arthritis presented with tense bullae and cutaneous fragility on the face and the back of the hands. In both, skin biopsy showed a cell-poor subepidermal vesicle with festooning of the dermal papillae. Direct immunofluorescence revealed staining at the dermal-epidermal junction and around blood vessels with IgG in the first case and with IgG, IgA, and fibrin in the second case. Urine collections and serum samples yielded normal levels of uro- and coproporphyrins.
CONCLUSIONS
Most cases of pseudoporphyria are drug-induced. Naproxen, the most common offender, has been associated with a dimorphic clinical pattern: a PCT-like presentation and one simulating erythropoietic protoporphyria in the pediatric population. Other NSAIDs of the propionic acid family can also cause pseudoporphyria.
Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Juvenile; Drug Eruptions; Female; Humans; Low Back Pain; Male; Naproxen; Oxaprozin; Photosensitivity Disorders; Porphyrias; Propionates; Skin Diseases, Vesiculobullous
PubMed: 10082597
DOI: 10.1177/120347549900300314 -
International Journal of Dermatology Mar 1999
Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Drug Eruptions; Humans; Male; Oxaprozin; Propionates; Shoulder Pain; Stevens-Johnson Syndrome
PubMed: 10208628
DOI: 10.1046/j.1365-4362.1999.00590.x -
Journal of Analytical Toxicology 1999
Topics: Anti-Inflammatory Agents, Non-Steroidal; Benzodiazepines; Drug Interactions; Humans; Immunoassay; Oxaprozin; Propionates; Receptors, GABA-A
PubMed: 10192417
DOI: 10.1093/jat/23.2.125 -
Clinical Therapeutics Jan 1999Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for the treatment of signs and symptoms of osteoarthritis (OA). Nabumetone and oxaprozin are 2 of... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for the treatment of signs and symptoms of osteoarthritis (OA). Nabumetone and oxaprozin are 2 of the newer NSAIDs and have been shown to have similar safety and efficacy profiles. Nabumetone 1000 mg to 1500 mg once a day (QD) and oxaprozin 1200 mg QD are commonly recommended doses. This study compared the health-related quality of life (HRQOL) of patients receiving oxaprozin 1200 mg QD with that of patients receiving nabumetone 1000 mg QD or nabumetone 1500 mg QD for the treatment of signs and symptoms of OA of the knee. Two similarly designed, independent, randomized, double-masked, placebo-controlled clinical trials were conducted. In trial 1, patients were randomized to receive oxaprozin 1200 mg QD (n = 109), nabumetone 1000 mg QD (n = 110), or placebo (n = 109); in trial 2, patients received oxaprozin 1200 mg QD (n = 116), nabumetone 1500 mg QD (n = 115), or placebo (n = 116). HRQOL was measured by the Medical Outcomes Study Short-Form-36 Health Survey (1-week recall period) at baseline and weeks 2 and 6. Data from the 2 trials were combined to assess differences across the 4 groups in 8 domains and 2 summary scores at baseline, and changes in HRQOL scores at weeks 2 and 6. At week 2, the oxaprozin group showed significantly greater improvement than the placebo group in role physical, vitality, and mental component summary (MCS) scores (P < 0.05), and in physical functioning, bodily pain, social functioning, and physical component summary (PCS) scores (P < 0.01). The nabumetone 1500-mg group showed significantly greater improvement than the placebo group in bodily pain and social functioning (P < 0.05), and in vitality and MCS score (P < 0.01). No significant differences were observed between the nabumetone 1000-mg and placebo groups. At week 2, the oxaprozin group showed a greater change than the nabumetone 1000-mg group in PCS score (P < 0.05). At week 6, oxaprozin treatment resulted in significantly greater improvement than placebo in physical functioning, role physical, and bodily pain (P < 0.05); social functioning, role emotional, and mental health (P < 0.01); and vitality and MCS score (P < 0.001). The nabumetone 1500-mg group showed significantly greater responses than the placebo group in vitality (P < 0.05), mental health (P < 0.01), and MCS score (P < 0.001). The oxaprozin group had significantly better scores than the nabumetone 1500-mg group in the PCS (P < 0.05), and it showed significantly greater improvement than the nabumetone 1000 mg group in role physical and PCS score (P < 0.01) and in role emotional (P < 0.05). No statistically significant differences were found between placebo and nabumetone 1000 mg at week 6. Results of this study suggest that oxaprozin 1200 mg QD has a significant positive impact on the HRQOL of patients with OA of the knee compared with nabumetone 1000 mg QD and placebo.
Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Butanones; Female; Humans; Male; Middle Aged; Nabumetone; Osteoarthritis, Knee; Oxaprozin; Propionates; Quality of Life; Randomized Controlled Trials as Topic; Sickness Impact Profile
PubMed: 10090436
DOI: 10.1016/S0149-2918(00)88279-X