Misoprostol clinical pharmacology. Establishment of activity in man.

Misoprostol has been evaluated in healthy subjects for both antisecretory and pharmacological activity. Doses used were determined initially from acute and chronic tolerance testing in healthy subjects. In the single dosage range of 50-200 micrograms, misoprostol inhibits gastric acid secretion in a dose-related manner both in the basal state and after stimuli such as histamine and standard test meals. The 200 micrograms dose differs significantly from placebo as an antisecretory agent. A preliminary study in six subjects suggested that the 400 micrograms dose does not produce a substantial increase in activity over the 200 micrograms dose. Furthermore, side-effects such as diarrhea and abdominal cramps appear to be dose related. The antisecretory action of misoprostol is maximal one hour after drug administration and is negligible after 4-5 hours. These factors have until now dictated a 50-200 micrograms q.i.d. dosing regimen for misoprostol in clinical trials against peptic ulcer. Misoprostol does not significantly affect platelet function in terms of ADP-, collagen- and thrombin-induced platelet aggregation. Measurements of FEV1, vital capacity, and peak expiratory flow rate have revealed that misoprostol has no significant bronchodilating or bronchoconstricting effect. Studies of endocrine function revealed only a slight rise within the normal range in serum cortisol in women.