Ranitidine kinetics and dynamics. I. Oral dose studies.

Area of Science:

• Pharmacology
• Gastroenterology

Background:

• Ranitidine is an H2-receptor antagonist known to decrease gastric acid secretion.
• The relationship between ranitidine serum concentration and its antisecretory effect requires further elucidation.

Purpose of the Study:

• To investigate the correlation between ranitidine serum concentration and the inhibition of pentagastrin-stimulated gastric secretion.
• To determine optimal dosing for therapeutic effect and assess safety.

Main Methods:

• Twelve healthy males received oral ranitidine (20, 40, or 80 mg) 90 minutes before a 3-hour pentagastrin infusion.
• Gastric hydrogen ion output, secretion volume, and pepsin activity were measured.
• Ranitidine serum concentrations were monitored and correlated with antisecretory effects.

Main Results:

• Ranitidine doses of 20, 40, and 80 mg reduced hydrogen ion output by 29%, 50%, and 70%, respectively.
• Peak serum ranitidine concentration positively correlated with reduced hydrogen ion output (r=0.81) and secretion volume (r=0.71).
• A 50% reduction in hydrogen ion output was associated with a peak serum concentration of 165 µg/L, achieved 60-120 minutes post-dose.

Conclusions:

• An 80 mg dose of ranitidine every 8 hours is suggested for effective therapeutic outcomes.
• Single doses of ranitidine showed no significant adverse effects.
• A decrease in white blood cell count observed in most subjects requires further investigation.