The present investigation was designed to determine the rate of development of tolerance during initiation of therapy with oral ISDN and the rate of tolerance reversal after withdrawal of this drug.
MethodsStudy population. Ten patients, nine men and one woman, ranging in age from 37 to 77 years (mean 56), with stable, exercise-induced angina pectoris were studied. Patients who had had previous exposure to ISDN or other oral or cutaneous nitrate preparations were not included. These patients had been taking nitroglycerin, but this was not used in the 24 hr before study and was not required in any patient during this period of investigation. Other exclusion characteristics included the presence of cardiomegaly, cardiac failure, cerebral vascular disease, hepatic disease, renal dysfunction, or the administration of fl-blocking agents or vasodilators. Patients were also excluded if they had a history of severe headaches or symptoms of postural hypotension after nitroglycerin administration.Study design Day 1. After an overnight fast, control measurements were made of heart rate and blood pressure with patients in the supine and standing positions, and a 5 ml sample of venous CIRCULATION Downloaded from http://ahajournals.org by on
Gallopamil is a calcium-channel antagonist with reported activity in experimental animals three to five times higher than that of verapamil. An automated high-performance liquid chromatographic (HPLC) method with fluorescence detection is described for the simultaneous determination of gallopamil and its metabolite norgallopamil in plasma. Gallopamil was well resolved from norgallopamil and other metabolites, allowing simultaneous quantitation of both drugs. The detection limit for both gallopamil and norgallopamil was 0.9 ng/ml. This method has been successfully used for the determination of gallopamil and norgallopamil following the administration of 25-, 37.5-, and 50-mg oral doses of drug.
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