Anti-secretory 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 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, t1/2 and clearances were independent of dose; however, AUC and Cmax 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.
Koss
M A
MA
Division of Gastroenterology, University of California at San Diego.
Hogan
D L
DL
Lane
J
J
Steinbach
J H
JH
Isenberg
J I
JI
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005744:Gastric Acid / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011899:Ranitidine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D012016:Reference Values; D012636:Secretory Rate / Q000187:drug effects
D011899:Ranitidine