Changes in upper gastrointestinalpH with aging: Implications for drug absorption.

Abstract

Upper gastrointestinal pH was compared in 43 healthy elderly with 24 healthy young subjects. Pre- and post-pr and ial pH was measured in the stomach and in the duodenum using a radiotelemetric technique. All young had acidic prepr and ial gastric pH, whereas 9% of elderly had elevated gastric pH and 7% were determined to be achlorhydrics. These incidences are somewhat lower than reported by other workers (values range from 12% to $>$50%), possibly because other studies were conducted on patients rather than healthy volunteers. Administration of a meal resulted in an elevation in gastric pH, from 1.7 to 5.0 in the young and from 1.4 to 4.9 in the elderly, and a reduction in duodenal pH from 6.1 to 5.4 in the young and from 6.6 to 5.8 in the elderly. In addition to the higher incidence of elevated fasted gastric pH, the postpr and ial pH in the stomach took significantly longer to return to pre-meal levels in elderly than in young subjects. Furthermore, duodenal pH was 0.3-0.5 pH units higher in elderly than in young subjects, irrespective of meal intake. The pH profiles for the young and elderly groups were then incorporated into a model for gastrointestinal drug absorption so that the effects of alterations in gastrointestinal pH with aging could be predicted. Mefenamic acid and dipyridamole were chosen as representative examples of a weak acid and a weak base respectively. The results of these simulations suggest that only modest changes in drug absorption occur in most elderly as a result of differences in pH, but that in those elderly with elevated pH ($\\sim$9% of healthy individuals), the changes in absorption may be therapeutically significant. Specifically, the absorption of mefenamic acid was predicted to be enhanced in the achlorhydric subjects in contrast with the large decrease of fraction absorbed predicted for dipyridamole, as dictated by dissolution rate changes with gastrointestinal pH.