Reversal of the tolerance phenomenon by the intermittent administration of a histamine H2-receptor antagonist.
OBJECTIVE
The attenuated antisecretory activity of H2-receptor antagonists (H2RA) during continuous administration is referred to as the tolerance phenomenon. A previous study indicated that Helicobacter pylori (H. pylori) infection prevents the occurrence of tolerance to H2RA. In the present study, we investigated whether intermittent (every other day) administration prevents the tolerance phenomenon in H. pylori-negative patients.


METHODS
Ten H. pylori-negative, healthy volunteers were included in the study. All of the patients underwent two courses of H2RA (lafutidine) administration: 21-day continuous administration (every day), followed by 21-day intermittent administration (every other day), with at least a 21-day lafutidine-free period between the first and second courses. All of the patients were examined by ambulatory intragastric pH monitoring five times: before medication, and on days 1 and 21 of the first (continuous) and second (intermittent) courses of lafutidine (10 mg b.d.) in a crossover fashion.


RESULTS
The continuous administration of lafutidine had a significantly attenuated, acid-suppressing effect in H. pylori-negative patients, and showed evidence of the tolerance phenomenon. However, the tolerance phenomenon was not observed through intermittent administration.


CONCLUSIONS
These results demonstrated that in H. pylori-negative patients, tolerance to H2RA, induced by continuous lafutidine administration, was reversed by subsequent intermittent administration.
Takahashi
Morio
M
Department of Gastroenterology and Hepatology, Dokkyo Medical University, Koshigaya Hospital, Saitama, Japan. mtak@dokkyomed.ac.jp
Katayama
Yasumi
Y
D000081:Acetamides / Q000008:administration & dosage*; D000328:Adult; D000897:Anti-Ulcer Agents / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D005744:Gastric Acid / Q000378:metabolism*; D005745:Gastric Acidity Determination; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D006635:Histamine H2 Antagonists / Q000008:administration & dosage*; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage*; D011725:Pyridines / Q000008:administration & dosage*; D013997:Time Factors
D000081:Acetamides; D000897:Anti-Ulcer Agents; D006635:Histamine H2 Antagonists; D010880:Piperidines; D011725:Pyridines; C076948:lafutidine