An open trial of naproxen in rheumatoid arthritis patients with significant esophageal, gastric, and duodenal lesions.

To confirm the reported lack of major gastrointestinal side effects of naproxen, we gave 58 patients with active rheumatoid arthritis and significant gastrointestinal disease therapeutic doses of naproxen while closely monitoring them for signs and symptoms of gastrointestinal dysfunction. All patients underwent upper gastrointestinal x-ray examinations at the start of the trail, and, when indicated, during the course of the study. Endoscopies were also performed when indicated. Forty patients had hiatus hernia and 35 had peptic ulcer (23 duodenal ulcer and 12 gastric ulcer). Twenty-six patients had a combination of hiatus hernia with either type of peptic ulcer. After 262 patient visits over a period of 52 weeks, 35 patients remained in the study, all having had more than six months of naproxen therapy in dosages ranging from 500 to 750 mg daily. In 33 of the 35, the response to naproxen had generally been good to excellent. Only seven patients dropped out of the trial because of complaints referable to side effects. There were no major related upper gastrointestinal side effects as monitored by continuing clinical evaluation, stool occult blood, comprehensive laboratory examination, and, where indicated, upper gastrointestinal x-ray studies. Approximately 70 per cent of the patients demonstrated efficacy on long-term naproxen therapy by subjective and objective parameters. Naproxen appears to be an efficacious and remarkably safe drug in the long-term therapy of rheumatoid arthritis, even in the presence of significant upper gastrointestinal symptomatology.

[Clinical-pharmacological and pharmacokinetic studies with naproxen]. / Klinisch-pharmakologische und pharmakokinetische Studien mit Naproxen

d-2-(6'-Methoxy-2'-naphthyl)-propionic acid (naproxen) is bound in blood to a high degree to plasma protein. After oral application naproxen is absorbed rapidly and completely. The mean biological half-life in man is fourteen hours. This gives us the possibility of controlling the symptoms of disease with two daily doses. In man, 99% of naproxen is excreted in the urine, either unchanged or glucuronized and as its 6-des-methyl metabolite. There is a linear increase of plasma levels with daily doses of up to 500 mg. Higher naproxen doses do not produce higher blood levels but lead to a faster excretion. This probably depends in part on a saturation of the binding sites in plasma. Differences in affinity of some compounds for binding sites in plasma are responsible for a potential interaction between naproxen and other agents, such as warfarin, acetyl salicylic acid (ASA) and sulfonylureas. These interactions are discussed. In a double-blind trial the influence of naproxen and ASA on the gastric mucosa of healthy volunteers has been compared. The results of gastroscopic findings as well as laboratory tests are reported.

[Long-term therapy of progressive chronic polyarthritis with naproxen]. / Langzeit-Therapie der progredient chronischen Polyarthritis mit Naproxen

The efficacy of d-2-(6'-methoxy-2'-naphthyl)-propionic acid (naproxen) in the treatment of patients with rheumatoid arthritis as well as its good tolerance has been established in double-blind studies which have been conducted in 34 centers in the U.S.A. Since the value of a new antirheumatic drug can only be assessed after years of clinical experience, provision was made in the protocols of the double-blind studies that the patients completing the controlled studies could continue naproxen treatment. Our experience is based on 603 patients, of whom 337 came from controlled, and 266 from previous open studies. The longest treatment with naproxen lasted four years. 16% of the patients discontinued therapy because of a exacerbation of their symptoms, and 8% because of side-effects, the latter being described in detail. Follow-up examinations of the patients were performed 4841 times at bi-monthly intervals. The statistical analysis of the objective disease symptoms showed a significant decrease of the rheumatic manifestations. In order to exclude the possibility of a long-term placebo effect, and as a proof of continuing efficacy, 73 patients received double-blind placebo instead of naproxen (placebo pulse) for two weeks, whereas the others continued on naproxen. Statistical analysis of the objective symptoms during the two treatment phases of the study showed naproxen significantly superior to placebo in all disease manifestations. Symptoms of those patients receiving placebo aggravated rapidly. They improved again after naproxen was resumed. The situation was reverse in those patients who received placebo during the second phase of the study. Side-effects were observed 13 times under placebo, but only two times under naproxen. The integration of a 2-week-placebo-pulse during long-term naproxen therapy of patients with rheumatoid arthritis is a sensitive method to prove the continuing therapeutic efficacy of this drug.