Plasma famotidine concentration versus intragastric pH in patients with upper gastrointestinal bleeding and in healthy subjects.

To study the concentration-response relationship of famotidine, we serially monitored intragastric pH and measured plasma drug concentrations simultaneously after an intravenous injection of this H2-receptor antagonist (0.1 mg/kg) in eight patients with upper gastrointestinal bleeding and in six healthy subjects. By applying the sigmoidal Emax model the mean (+/- SD) plasma famotidine concentrations associated with an intragastric pH of 4.0 in patients and healthy subjects were estimated to be 17.7 +/- 10.7 and 24.8 +/- 10.3 ng/ml, respectively (not significantly different). No significant differences were observed in the mean pharmacokinetic parameters between the two study groups. Multiple regression analysis revealed that not only a pharmacokinetic factor (i.e., elimination t1/2) but also a pharmacodynamic (or sensitivity) factor (i.e., a drug concentration associated with an intragastric pH of 4.0) contributed significantly (p less than 0.01) to the overall variability in the duration of antisecretory effect in our study subjects, with standardized partial regression coefficients of 0.54 and -0.63, respectively. Based on these data, we predict that around-the-clock control of a fasting intragastric pH above 4.0 can be attained by a continuous infusion of famotidine at rates ranging from 6 to 25 mg/day (mean +/- SD, 11 +/- 7 mg/day) in a 70 kg patient whose pharmacokinetic and pharmacodynamic characteristics are similar to those of our patients.