THE EFFECTS OF LOPERAMIDE HYDROCHLORIDE ON THE BOWEL MOVEMENTS OF HEALTHY PERSONS: Estimation of CD50 with the Up-and-down Method, and Pharmacokinetic Analysis of Blood Concentration of the Drug

The 50% constipation dose (CD50) to healthy volunteers of loperamide hydrochloride, a new synthetic antidiarrheal agent, was statistically estimated using the up-and-down method. At the same time, effects of the drug on subjective symptoms, laboratry findings were observed. Furthermore, plasma concentration were determined using radioimmunoassay in some volunteers. As a result of it, CD50 in two groups of healthy volunteers was 3.2mg/day and 6.96mg/day respectively. As concerns subjetive symptoms, sensation of fullness, rumbling and abdominal pain were observed more frequently and severely in a subject in whom constipation was induced. Apart from abdominal symptoms, drowsiness was complained in two subjects. The plasma concentrations of loperamide at the steady state during repeated intake of the drug every 24 hours were 0.5, 1.5, and 2.7ng/ml at daily intake of 2, 4, and 8mg respectively.