Nine healthy, male subjects received controlled-rate i.v. infusions of a new formulation of pirenzepine to produce constant plasma levels of 40 ng/ml and 105 ng/ml. They also received stepped infusions resulting in plasma levels of 20, 40, 80 and 40 ng/ml for defined periods. Peptone-stimulated gastric acid and volume secretion and near point vision decreased dose dependently, whereas gastric acidity was unchanged. There was a significant correlation between inhibition of gastric acid secretion and the pirenzepine concentration in plasma and in gastric juice. During the stepped i.v. infusion, changes in near point vision were closely related to the plasma drug concentration. Antimuscarinic side-effects occurred more frequently when the plasma drug level was high. Overall, there was a close relationship between the plasma concentrations and the effects and side-effects of pirenzepine. Its gastric inhibitory action was characterized only by a reduction in gastric volume secretion. Increasing plasma concentrations during the first days of treatment may be essential for its efficacy as an antiulcer drug.
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