Do continuous infusions of omeprazole and ranitidine retain their effect with prolonged dosing?
OBJECTIVE
Prolonged infusions of H2-antagonists are commonly used in intensive care units, although little is known about their antisecretory efficacy beyond the initial 24 hours of dosing. The aim of this study was to assess the antisecretory effects of infusions of ranitidine and omeprazole for a period of 72 hours.


METHODS
Twelve healthy volunteers received individually titrated 72-hour intravenous infusions of omeprazole, ranitidine, or placebo in a double-blind, crossover study. Gastric pH and dosing requirements were compared.


RESULTS
The median percentage of time with pH > 4 (interquartile range) was 93% (88%-95%) on day 1 and 96% (94%-99%) on day 3 with omeprazole and 67% (56%-78%) and 43% (31%-51%), respectively, with ranitidine (both P < 0.001 vs. omeprazole). The mean doses (+/- SD) required on days 1 and 3 for omeprazole were 235.8 +/- 44 mg and 134.0 +/- 37 mg (P < 0.0001), and ranitidine doses were 502.5 +/- 76 mg and 541.8 +/- 25 mg, respectively (P = 0.05).


CONCLUSIONS
Omeprazole infusions consistently maintained gastric pH above 4 over a period of 72 hours with progressively lower doses. Significant tolerance to the antisecretory effect of ranitidine infusion developed in 72 hours, which was not overcome despite individually titrated doses of more than 500 mg/24 hours. Consequently, application of pharmacodynamic results of single-day H2-blocker and proton-pump inhibitor studies to prolonged infusion trials for stress ulcer-related bleeding is inappropriate.
Merki
H S
HS
Department of Medicine, Inselspital, University of Bern, Switzerland.
Wilder-Smith
C H
CH
D000143:Acids / Q000378:metabolism; D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007260:Infusion Pumps; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009853:Omeprazole / Q000008:administration & dosage* / Q000494:pharmacology; D011899:Ranitidine / Q000008:administration & dosage* / Q000494:pharmacology; D013997:Time Factors
D000143:Acids; D011899:Ranitidine; D009853:Omeprazole