Day-Night and Individual Differences in Response to Constant-Rate Ranitidine Infusion

Abstract

Twelve ulcer patients with inactive disease received constant-rate infusions of ranitidine, in doses of 6.25 and 10.0 mg/hr, during separate 24-h spans. Gastric pH and serum ranitidine concentrations were monitored. Serum ranitidine concentrations did not vary significantly after attainment of steady-state. For the group, gastric acidity was controlled above pH 4 during the day; however, at night, when gastric acid secretion was greatest under placebo conditions, ranitidine less effectively controlled gastric pH. There was individual variation in response to ranitidine. Patients (8/12) evidencing control of gastric acidity (pH ± 4) for at least 16 h when infused with ranitidine (6.25 mg/h) were considered re-sponders. Those (4/12) not so well controlled were designated poor responders. With parenteral infusion of 6.25, as well as 10.0 mg/h ranitidine, responders evidenced a relatively high 24-h mean pH and only minor day-night variation in gastric acidity. In contrast, poor responders were characterized by a low 24-h mean pH and high-amplitude circadian variation in gastric acidity. Poor responders evidenced statistically significant (p < 0.05) lower gastric pH responses to parenteral infusions than did responders. A similar, significant difference between the two groups was observed when the percentage of time that gastric pH was maintained below 4 was considered. Differences between responders and poor responders to ranitidine infusion are unknown. Since Zollinger-Ellison syndrome patients were not included in the study, observed differences in drug response cannot be ascribed to hypersecretion of gastric acid.

Key Words:

• Circadian rhythm
• Ranitidine
• Intravenous infusion
• Ulcer
• Responder
• Nonre-sponder