ANTISECRETORY EFFECTS AND PHARMACOKINETICS OF LOW-DOSE RANITIDINE

The purpose of this study was to examine the anti-secretory effect of low doses of orally administered ranitidine on meal-stimulated gastric acid secretion and assess its pharmacokinetics. The effect of 20, 40, 60 and 80 mg of ranitidine p.o. and placebo were tested on 5 separate days (Latin square, double-blind) in 15 healthy males (mean age 35 ye ars). Gastric acid secretion was measured prior to and for 8 h followi ng two sequential mixed liquid meals administered at 4-h intervals. Ve nous blood samples were obtained at frequent intervals before and foll owing each dose for determination of plasma ranitidine concentration b y high pressure liquid chromatography. Each dose of ranitidine signifi cantly (P < 0.01) decreased the peak and cumulative 4-h acid secretory responses to the first meal (range 58-93%), and the 60 and 80 mg dose s significantly inhibited the response to the second meal by 31 and 43 %, respectively. Total 8-h meal-stimulated acid outputs were decreased significantly in a dose-related manner (range 38-73%). Peak plasma ra nitidine occurred approximately 1 h after dosing. Ranitidine t(max), t 1/2 and clearances were independent of dose, however, AUC and C(max) w ere dose-related. Inhibition of acid secretion was related to plasma r anitidine concentration; the mean IC50 was 27 (+/- 6.4) ng/ml. We conc lude that modest doses (equivalent to 7-27% of the daily therapeutic d ose) of ranitidine effectively suppress meal-stimulated gastric acid s ecretion in a dose-related manner. If these doses are of clinical effi cacy, it may be possible for substantial cost savings to occur.