Abstract
Upon oral administration of nitroglycerin-proxy-phylline tablets with timed release to humans, it was observed that the nitroglycerin blood levels declined after the 5th day. Experiments in rabbits and mice were performed to clarify whether this phenomenon is caused by enzyme induction. Oral administration of 0.1 and 0.2 mg./kg. nitroglycerin to rabbits caused a decrease in the peripheral maximal temperature rise. The decline in pharmacological action depends on dosage and apparently follows first-order kinetics. Pretreatment of mice with either nitroglycerin or pentobarbital caused a similar decrease in pentobarbital sleeping time, indicative of enzyme induction. However, in contrast to the hepatic response elicited by barbiturate pretreatment in which the liver weights increased, nitroglycerin caused a significant decrease, thereby suggesting a different mechanism of action for the vasodilator.
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