effects of loperamide on pancreaticobiliary functions are Loperamide, a peripherally acting opiate receptor agonist poorly investigated. Inhibition of gallbladder emptying or with antidiarrheal action, inhibits ileal and colonic motor pancreatic enzyme secretion by loperamide may have imfunction. It was determined whether loperamide also affects portant clinical implications because stasis of bile is a major gallbladder emptying and pancreatic enzyme secretion in hufactor contributing to the formation of gallstones 6-10 and bemans. Plasma cholecystokinin (radioimmunoassay), gallbladcause impairment of pancreatic enzyme secretion may induce der volume (ultrasonography), and intraduodenal bilirubin or aggravate maldigestion. 11-13 and amylase output (spot sampling) were measured at regular
The aim of this study, therefore, was to determine the intervals before and during intraduodenal perfusion of an effect of loperamide on basal and meal-stimulated gallbladder amino acid meal in 8 healthy subjects: once without and once motility and pancreatic enzyme secretion in healthy volunwith pretreatment of 8 mg loperamide, ingested 13 and 4
teers. Gallbladder emptying and pancreatic enzyme secretion hours before the start of the meal. Loperamide decreased were studied in response to an intraduodenal amino acid basal amylase output from 3.2 { 0.5 to 1.0 { 0.5 kU/h meal to circumvent possible influences of loperamide on gas-
P รต .005) and abolished basal bilirubin output (21 { 5 vs. tric emptying or on the digestion of nutrients. 14 0 { 0 mmol/h; P รต .005) into the duodenum. Loperamide increased basal gallbladder volume from 28 { 4 to 39 { 4 PATIENTS AND METHODS mL (P รต .0001) but was without effect on basal plasma cholecystokinin (2.7 { 0.3 vs. 3.0 { 0.3 pmol/L). During Subjects. Eight healthy volunteers (3 women and 5 men; age the amino acid meal, pretreatment with loperamide inhibited range, 19-27 years) participated in the studies. None of the volun- amylase output from 5.1 { 0.8 to 1.6 { 0.4 kU/h (P รต .001), teers was taking any medication or had a history of gastrointestinal bilirubin output from 39 { 6 to 18 { 6 mmol/h (P รต .0005) symptoms or surgery. The study protocol was approved by the and gallbladder contraction from 47% { 3% to 26% { 6% ethical committee of the University Hospital Nijmegen, and all sub- (P รต .05), whereas loperamide enhanced amino acid-stimujects gave their written informed consent before entering the study. Reagents. Loperamide chloride was obtained from Janssen Phar-lated plasma cholecystokinin from 4.5 { 1.6 to 7.6 { 1.0 maceutica (Beerse, Belgium). Radioiodinated porcine pancreatic pmol/L (P รต .05). It is concluded that loperamide inhibits polypeptide was obtained from Novo Nordisk AS (Bagsvaerd, Denbasal and amino acid-stimulated gallbladder motility and mark). Synthetic CCK 33 was from Peninsula Laboratories Europe, intraduodenal output of bilirubin and amylase, despite an Ltd. (St. Helens, England). 125 I-hydroxyphenyl propionic acid-sucenhanced postprandial cholecystokinin release. (HEPATOLcinimide ester (Bolton-Hunter reagent) was obtained from New OGY 1997;26:256-261.) England Nuclear Corp. (Boston, MA). Pharmacia Decanting Suspension no. 3 was from Pharmacia Diagnostics, AB (Uppsala, Sweden). Human pancreatic polypeptide and L-amino acids were from Sigma Loperamide is widely used for the treatment of patients Chemical Co. (St. Louis, MO). Polyethylene glycol 4000 (PEGwith diarrhea resulting from a variety of diseases. 1,2 Dosages 4000) from BDH, Ltd. (Poole, England). All other materials were used to treat acute or chronic diarrhea vary from 2 to 16 mg obtained from Merck (Amsterdam, The Netherlands).
daily. 1 Recently, even higher dosages have been recom-Study Protocol. After a 12-hour fast, the volunteers presented at mended. 2 Loperamide probably exerts its antidiarrheal action the laboratory at 7:30 am. In random order, two experiments were by a change in motor function of the intestine, resulting in performed separated from each other by at least 1 week. At the an increased capacitance of the gut and a delay in the passage beginning of each test a double-lumen polyvinyl tube with an OD of fluid through the intestine. 1,3 Some studies also suggest of 5.7 mm was placed in the duodenum. The proximal lumen of the tube was positioned at the level of the papilla Vateri, and the antisecretory effects of the drug at the intestinal level. The distal lumen was positioned at the ligament of Treitz. The position of the tube was verified by fluoroscopy. In addition, an in-dwelling intravenous catheter was placed in a forearm. The catheter was kept Abbreviations: PEG-4000, polyethylene glycol 4000; CCK, cholecystokinin.
patent by a heparine-saline solution and was used for the collection From the Departments of 1 Gastroenterology and Hepatology, 2 Clinical Chemistry, of blood samples. After an equilibration period of at least 30 minand