I The properties of a recently introduced digitalis glycoside, 4-,-methyl digoxin (medigoxin)were compared to those of a standard digoxin preparation. Using a radioimmunoassay (RIA) technique, serial plasma levels were recorded for 8 h following a single oral dose in five fasting volunteer subjects, and urinary glycoside elimination was measured for 4 consecutive days after dosage by use of a modification of the RIA method. 2 It was found that this RIA was suitable for plasma level measurement of both digoxin and midigoxin by reference to appropriate standard curves. Comparison of the plasma level profiles of these two drugs showed that medigoxin was very rapidly absorbed with peak levels occurring within 15-30 min, while digoxin produced peak levels after 45-75 min. The area under the plasma level-time curve produced by medigoxin was also consistently greater than that produced by digoxin, even though the medigoxin dose used was smaller. Quantitative comparison of these areas after adjustment to compensate for differing doses showed that medigoxin is considerably more biologically available than digoxin under study conditions (ratio 1.6 + 0.25: 1), and comparison of quantitative urinary elimination suggested that medigoxin is eliminated in the urine to a lesser extent than digoxin and therefore it undergoes more metabolism and/or hepato-biliary elimination.
The effects on coronary dynamics of propranolol and atenolol were studied in 12 patients undergoing cardiac catheterisation for suspected coronary artery disease. Myocardial blood flow was measured using the coronary sinus continuous thermodilution technique. Data were obtained immediately after drug administration and during rapid atrial pacing. The immediate effects were similar for both drugs. A significant reduction in heart rate was accompanied by a small reduction in myocardial oxygen consumption. Changes in coronary sinus flow induced by rapid pacing were closely related to changes in tension-time index. This relation was not modified by propranolol or atenolol. Neither propranolol nor atenolol therefore has significant coronary vasoconstrictor properties. Cardioselectivity appears to be unimportant with respect to beta-adrenergic blockade and the coronary circulation.
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