Smoking and pH Response to H₂-Receptor Antagonists

Smoking has been shown to impair the therapeutic effect of H2-receptor antagonists. To evaluate the acid-reducing capacity of H2-receptor antagonists in relation to smoking habits, we tested the effect of ranitidine (Ran) and famotidine (Fam) under physiologic conditions, using ambulatory pH-metry. Intragastric pH was measured over 20 h. Each of 18 healthy volunteers, 9 smokers and 9 nonsmokers, received 40 mg Fam, 300 mg Ran, or placebo in a double-blind, randomized study as a single evening dose. With both drugs 20-h acidity was markedly suppressed. After Fam treatment mean inhibition was 61% in smokers and 76% in nonsmokers and after Ran 51% and 67%, respectively. When areas under the pH curves for each individual were calculated and treatment compared with placebo (= 100%), the response was smaller in smokers than in nonsmokers with either drug (Fam, 153 +/- 21% versus 214 +/- 19%, p less than 0.01; Ran, 176 +/- 21% versus 232 +/- 29%, p less than 0.05) during the first 4 h after drug intake. A similar effect was observed in the morning period from 0600 to 1000 h (Fam, 118 +/- 19% versus 206 +/- 19%, p less than 0.001; Ran, 133 +/- 21% versus 207 +/- 31%, p less than 0.02). During the nighttime there were no significant differences. These findings indicate that smoking impairs the response to both drugs tested.