Absence of tolerance in duodenal ulcer patients treated for 28 days with a bedtime dose of roxatidine or ranitidine.
There is much experimental work on the occurrence of tolerance to the antisecretory effect of H2-receptor antagonists in healthy subjects, while data on its development in patients with duodenal ulcer are poor and conflicting. Moreover, this phenomenon has not been studied previously with 24 h gastric pH-metry in patients with active duodenal ulcer. For these reasons, we carried out a prospective pharmacodynamic investigation in 48 patients with endoscopically proven duodenal ulcer using the well-established once daily dosing schedule of H2 blockers. They were studied by means of 24 h continuous endoluminal pH-metry which was performed before, on d1 and d28 after receiving an oral bedtime dose (2200 hours) of either roxatidine 150 mg or ranitidine 300 mg, given in randomized and single-blind fashion. Eight patients did not complete the study for various reasons and 82% of ulcers healed after 4 weeks of therapy. Gastric pH was higher (P < 0.001) on d1 and d28 than basal values during all time periods, but the evening, with both H2 blockers. There was no significant difference between pH values of d1 and d28 in any time interval with both roxatidine and ranitidine. There was also no difference in pharmacodynamic data between the two active treatments. We conclude that tolerance does not develop after 1 month's treatment with a bedtime dose of H2 antagonist in patients with active duodenal ulcer and therefore data gathered on this phenomenon in healthy subjects are not applicable to ulcer patients.
Savarino
V
V
Dipartimento di Medicina Interna, Cattedra di Gastroenterologia, Università di Genova, Italy.
Mela
G S
GS
Zentilin
P
P
Cutela
P
P
Vigneri
S
S
Termini
R
R
Di Mario
F
F
Ferrana
M
M
Malesci
A
A
Belicchi
M
M
Celle
G
G
D000328:Adult; D000704:Analysis of Variance; D004361:Drug Tolerance; D004381:Duodenal Ulcer / Q000188:drug therapy*; D005260:Female; D005745:Gastric Acidity Determination; D006635:Histamine H2 Antagonists / Q000008:administration & dosage*; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage*; D011446:Prospective Studies; D011899:Ranitidine / Q000008:administration & dosage*; D016037:Single-Blind Method
D006635:Histamine H2 Antagonists; D010880:Piperidines; D011899:Ranitidine; C053742:roxatidine acetate