Comparison of the effects of immediate-release omeprazole powder for oral suspension and pantoprazole delayed-release tablets on nocturnal acid breakthrough in patients with symptomatic gastro-oesophageal reflux disease.

BACKGROUND: Many patients treated with a proton-pump inhibitor for gastro-oesophageal reflux disease or erosive oesophagitis still have substantial night-time gastric acidity. A previous trial of a new immediate-release omeprazole oral suspension suggested that nocturnal gastric acidity could be more effectively controlled with a bedtime dose of immediate-release omeprazole than with a delayed-release proton-pump inhibitor administered before dinner or at bedtime. AIM: To compare the ability of immediate-release omeprazole with pantoprazole to control nocturnal gastric acidity, when they were dosed once daily and twice daily. METHODS: Thirty-six patients with nocturnal gastro-oesophageal reflux disease symptoms received immediate-release omeprazole and pantoprazole in this open-label, randomized-crossover trial. Median gastric pH, the percentage of time with gastric pH > 4 and the percentage of patients with nocturnal acid breakthrough, were evaluated with 24-h pH monitoring. RESULTS: Repeated once daily (bedtime) dosing with immediate-release omeprazole suspension produced significantly better nocturnal gastric acid control than repeated once daily (predinner) or twice daily (prebreakfast and bedtime) dosing with pantoprazole delayed-release tablets (median pH: 4.7 vs. 2.0 and 1.7; percentage of time pH > 4: 55 vs. 27 and 34; nocturnal acid breakthrough: 53 vs. 78 and 75). Twice daily dosing (prebreakfast and bedtime) with immediate-release omeprazole 20 and 40 mg achieved the best night-time control of gastric acidity. Repeated once daily bedtime dosing with immediate-release omeprazole 40 mg and twice daily dosing with pantoprazole 40 mg gave similar 24-h pH control. No safety issues were associated with either drug in this trial. CONCLUSIONS: Dosed once daily at bedtime, immediate-release omeprazole reduced nocturnal gastric acidity to a degree not observed with once daily dosing of delayed-release proton-pump inhibitors.

Pilocarpine tablets for the treatment of dry mouth and dry eye symptoms in patients with Sjögren syndrome: a randomized, placebo-controlled, fixed-dose, multicenter trial. P92-01 Study Group.

BACKGROUND: Patients with Sjögren syndrome (SS) experience slowly progressive infiltration of lacrimal and salivary glands by mononuclear cells. This leads to diminished secretions, with resultant symptoms of xerostomia and xerophthalmia. Although pilocarpine hydrochloride tablets are currently indicated for the treatment of radiation-induced xerostomia, their effects on dry mouth or dry eyes in patients with SS are unclear. OBJECTIVE: To assess the safety and efficacy of pilocarpine (Salagen) tablets as symptomatic treatment for dry mouth and dry eyes caused by SS in a multicenter, doubleblind, placebo-controlled trial. METHODS: After providing written informed consent, 373 patients with primary or secondary SS and clinically significant dry mouth and dry eyes were randomized to receive 2.5-mg pilocarpine, 5-mg pilocarpine, or placebo tablets 4 times daily for 12 weeks. Symptoms were assessed by questionnaires with visual analog scales or categorical checkboxes. Whole-mouth salivary flow rates were measured. RESULTS: A significantly greater proportion of patients in the 5-mg pilocarpine group showed improvement compared with the placebo group (P< or =.01) in global assessments of dry mouth, dry eyes, and other symptoms of dryness (P< or =.05). Salivary flow was significantly increased 2- to 3-fold (P<.001) after administration of the first dose and was maintained throughout the 12-week study. The most common adverse effect was sweating, and no serious drug-related adverse experiences were reported. CONCLUSION: Administration of 5-mg pilocarpine tablets 4 times daily (20 mg/d) was well tolerated and produced significant improvement in symptoms of dry mouth and dry eyes and other xeroses in patients with SS.

Developing nonsteroidal anti-inflammatory drugs (NSAIDs) with decreased gastrointestinal (GI) toxicity.

NSAID-induced gastropathy is an important iatrogenic disorder that must be addressed in the development of NSAIDs. A scheme for clinical evaluation is described and salsalate is discussed as a prototype.

Reduced risk of NSAID gastropathy (GI mucosal toxicity) with nonacetylated salicylate (salsalate): an endoscopic study.

This randomized, investigator-blinded, parallel group endoscopic study evaluated the effects of salsalate and naproxen on the gastroduodenal mucosa over a 3-month period in patients with RA. Using therapeutic doses of the drugs, 8 of 21 patients (38%) in the naproxen group had endoscopically shown active ulcers (seven patients) or diffuse erosions (one patient), whereas none of the 18 patients treated with salsalate (0%) had such lesions (P = .003). Five of the eight naproxen-treated patients with evidence of GI damage were asymptomatic at the time of endoscopic verification of their lesions. The most significant disadvantage of salsalate was its higher incidence of otologic problems accounting for six of the nine discontinuations with salsalate. However, the findings of this study suggest that patients receiving salsalate are at lower risk for developing significant gastropathy than those treated with naproxen. The relative benefit-to-risk ratio of salsalate indicates that this drug should be considered as a significant alternative NSAID therapy.

Does the acetyl group of aspirin contribute to the antiinflammatory efficacy of salicylic acid in the treatment of rheumatoid arthritis?

In a multicenter, double-blind, parallel-group study, 233 patients with classical or definite RA who demonstrated disease flare during a prestudy washout period were randomized to 12 weeks of treatment with either the nonacetylated salicylate, salsalate (salicylsalicylic acid), or aspirin. Of the 150 patients who completed the study, 83 received salsalate and 67 were treated with aspirin. Doses of the two drugs were calculated to provide equal amounts of bioavailable salicylic acid. The efficacy of salsalate and aspirin, as measured by all the usual variables, was equivalent but aspirin-treated patients had a higher incidence of severe gastrointestinal problems. Thus, this study demonstrated that the acetyl group of aspirin does not enhance the anti-inflammatory efficacy of salicylic acid in RA.

An endoscopic comparison of the gastroduodenal injury seen with salsalate and naproxen.

Forty endoscopically normal healthy subjects were randomized to receive either BID salsalate (3500 mg/day) or BID naproxen (750 mg/day) for 14 days followed by repeat endoscopic examination. Gastroduodenal lesions were found in 55% (11/20) of the subjects taking naproxen, and 10% (2/20) of those taking salsalate (p = 0.002). Twenty-five percent (5/20) of the subjects taking naproxen and none of the subjects taking salsalate were noted to have severe gastric injury (p = 0.003). There was no difference between the 2 groups in subjective gastrointestinal system adverse experiences. Overall, 95% (19/20) of subjects taking salsalate reported at least 1 adverse experience compared with 60% (12/20) of those taking naproxen (p = 0.02). This was due primarily to the higher number of subjects taking salsalate reporting reversible tinnitus or hearing loss. There was no significant treatment difference in adverse experiences reported for any other organ system. The results of our study support previous observations in patients with rheumatoid arthritis that salsalate produces less gastroduodenal mucosal toxicity than the widely used antiinflammatory agent, naproxen.