Anti‐secretory effects and pharmacokinetics of low dose ranitidine

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Abstract
SUMMARY: 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 years). Gastric acid secretion was measured prior to and for 8 h following two sequential mixed liquid meals administered at 4‐h intervals. Venous blood samples were obtained at frequent intervals before and following each dose for determination of plasma ranitidine concentration by high pressure liquid chromatography. Each dose of ranitidine significantly (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 doses 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 ranitidine occurred approximately 1 h after dosing. Ranitidine tmax, t½ and clearances were independent of dose; however, AUC and C. were dose‐related. Inhibition of acid secretion was related to plasma ranitidine concentration; the mean IC50 was 27 (± 6.4) ng/ml. We conclude that modest doses (equivalent to 7–27% of the daily therapeutic dose) of ranitidine effectively suppress meal‐stimulated gastric acid secretion in a dose‐related manner. If these doses are of clinical efficacy, it may be possible for substantial cost savings to occur.