| Abstract: | In recent years there have been some reports of tolerance occurring in man with the antisecretory effect of H2 antagonists. We, therefore, studied the effect of 300 mg and 600 mg ranitidine (CAS 66357-35-5) daily and increasing i.v. doses of pentagastrin (0.37 microgram/kg, 0.75 microgram/kg, and 1.5 micrograms/kg body weight) on gastric acid output (mmol HCl/30 min) in 9 healthy volunteers. The study design was double-blind, randomized and cross-over. Pentagastrin stimulation was performed on day 1, day 8, and day 16. Increasing i.v. doses of pentagastrin induced an almost identical enhancement of volume secretion, total acid output as well as titratable acidity on the 3 study days. A 16-days treatment period with 300 mg and 600 mg ranitidine led to 80% and 90% inhibition of pentagastrin stimulated acid output. The degree of inhibition evoked by 300 mg and 600 mg ranitidine against pentagastrin was not statistically different during the 16-days treatment period; i.e. no significant tolerance did occur within 16 days. Our data suggest that, in contrast to intragastric acidity measurements, no significant decline of inhibitory effectiveness of ranitidine against i.v. pentagastrin could be observed in healthy male volunteers. |
