The safety profile of nonprescription ibuprofen in multiple-dose use: a meta-analysis.

A meta-analysis was performed to compare the incidence of adverse experiences (AEs) during the multiple-dose use of nonprescription ibuprofen to a placebo. Eight studies, with doses ranging from 800 to 1200 mg/day and durations of 1 to 10 days, met the criteria for inclusion. AEs were classified according to COSTART, except that "abdominal pain" was conservatively reassigned to the digestive system. In each study, the overall AE frequency among ibuprofen-treated subjects (n = 1094) was numerically less than or equal to the placebo (n = 1093). Pooled across all studies, placebo subjects reported AEs significantly (p = 0.018) more often (31.7%) than ibuprofen subjects (27.4%). The frequency of digestive system AEs was comparable (p = 0.420) for the placebo (11.0%) and ibuprofen (12.1%); there was no significant difference for any specific digestive system AE. AE frequency in the "body-as-a-whole" category was significantly higher (p < 0.001) in the placebo (20.4%) than in ibuprofen (14.8%). The number of severe AEs in all of these categories was lower for ibuprofen than for the placebo. These data indicate that nonprescription ibuprofen has an excellent side effect profile in multiple-dose use, with a frequency of gastrointestinal AEs comparable to a placebo.

Propranolol-hydralazine combination in essential hypertension.

The efficacy of a propranolol-hydralazine combination tablet was compared with that of each of its two components in the twice-daily treatment of mild to moderate essential hypertension (diastolic blood pressure: 100 to 125 mmHg). After a three-week, single-blind, placebo period, a 9- to 18-week, single-blind, dose-finding phase with the combination was performed. The daily doses of propranolol/hydralazine were 40 mg/25 mg, 80 mg/25 mg, 80 mg/50 mg, 120 mg/50 mg, 160 mg/50 mg, and 160 mg/100 mg. Of 83 patients, 73 (88%) had decreases in diastolic blood pressure equal to or greater than 10 mmHg. Thirty-eight (46%) patients had a diastolic blood pressure equal to or less than 90 mmHg while taking 80 mg propranolol/50 mg hydralazine or less given BID. Mean systolic and diastolic pressures were reduced by 16.8 mmHg (10.9%) and 17.6 mmHg (16.7%), respectively (P less than 0.001). A ten-week, double-blind, parallel-treatment phase followed in which patients were randomly assigned to the combination tablet or to propranolol or hydralazine. There were significantly larger increases in mean systolic (P less than 0.01) and mean diastolic (P less than 0.03) blood pressure when the components were taken alone than with the combination from the mean of the last three weekly dose-finding visits to the mean of the last four biweekly parallel-treatment visits. The changes in systolic/diastolic blood pressures were: hydralazine (n = 30), 14.43/8.62 mmHg; propranolol (n = 24), 9.87/6.09 mmHg; and the combination (n = 27), 1.47/1.53 mmHg. During the parallel-treatment phase, the proportions of patients with new complaints were: hydralazine, 16/31 (52%); propranolol, 10/25 (40%); and the combination, 11/27 (41%). In the hydralazine group, three patients had cardiovascular events (severe tachycardia, mild palpitations, and skipped heart beats) and two patients had mild anxiety; no such occurrences were noted in the propranolol or combination group. The mean change (increase) in heart rate from the end of dose-finding to the end of the double-blind period was significantly larger for patients taking hydralazine than for patients taking propranolol or the combination. Mean changes for these groups were: hydralazine, 12.4 beats/min; propranolol, 2.9 beats/min; and the combination, 1.8 beats/min (P = 0.0001). This study found the combination of propranolol plus hydralazine to be safe and more effective than either component.

Determination of nitrites in meat systems: An improved procedure.

Various analytical methods for nitrite determination in meat products, based on extraction of the preservative through digestion at 60-80 °C followed by colorimetric analysis gave relatively poor recoveries (44-65%) when applied to raw beef. An improved procedure was developed based on disintegration and dispersion of beef with sand prior to the extraction step and on the use of a higher concentration of N-(1-naphthyl) ethylenediamine dihydrochloride than normally used. The proposed technique resulted in almost 93% recovery of nitrites and showed a high precision revealed in a variation coefficient of 8̃%.