The antiarrhythmic effect of timolol was investigated in 160 subjects with supraventricular arrhythmias. In our double-blind, randomized, parallel, multiclinic study, subjects received timolol, 1 mg iv, or matching placebo as a starting dose, followed by a second and third dose of 1 mg each (or matching placebo) at 20-min intervals if the arrhythmia did not convert to sinus rhythm. Subjects in whom the sinus rhythm returned or the ventricular rate decreased to less than 100 bpm were transferred to a dosing regimen of timolol in 10-mg tablets twice a day by mouth, 1 hr after the last intravenous dose. Data indicated that the mean decrease in heart rate was 44 bpm after timolol and 7 bpm after placebo. The overall proportion of responders (either conversion to sinus rhythm or a decrease in ventricular rate to less than 100 bpm) was 68% after timolol and 7% after placebo. The proportions of responders after timolol were significantly higher than the proportions after placebo for paroxysmal supraventricular tachycardia (26 of 32 subjects and two of 38 subjects), atrial fibrillation (17 of 29 subjects and three of 32 subjects), and atrial flutter (seven of 11 subjects and one of nine subjects). The most common adverse effects were bradycardia and hypotension.
This study compared the effects of diet and cimetidine on theophylline metabolism and examined interactions between these effects. Twelve men received a high-protein diet for 15 days and at another time a high-carbohydrate diet also for 15 days. Cimetidine, 800 mg daily at bedtime, was administered on days 10 through 15 of each dietary period. Theophylline metabolism was studied after the administration of a single intravenous 3 mg/kg dose on days 8 and 15 of each dietary period. Changing from a high-protein to a high-carbohydrate diet decreased theophylline clearance by about the same extent (30% +/- 10%) as treatment with cimetidine (37% +/- 5% during a high-protein diet and 30% +/- 5% during a high-carbohydrate diet). Cimetidine did not significantly influence the effects of diet on theophylline clearance. Conversely, dietary composition did not influence the degree of inhibition of theophylline metabolism induced by cimetidine. Depending on the direction of the change in protein/carbohydrate ratio, the effects of diet and cimetidine treatment were either additive (theophylline clearance was most prolonged during the high-carbohydrate regimen with concurrent cimetidine administration) or counteractive (increasing the dietary protein/carbohydrate ratio at least partially counteracted the inhibitory effect of cimetidine). In individual subjects, effects of cimetidine on theophylline metabolism were somewhat more consistent than diet-induced changes. The results are further evidence that diet and drugs can have similar effects on hepatic drug metabolism rates in humans. Variations in diet over time and individual differences in responses to diet may provide the potential for considerable instability of drug metabolism rates in free-living subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
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