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PubMed1998

Effects of loperamide on ileoanal pouch function.

BACKGROUND: Opioid analogues are used to manage increased bowel frequency in patients with an ileoanal reservoir. The aim of the study was to determine the clinical efficacy of loperamide in patients with an ileoanal reservoir and to assess its effect on pouch motility. METHODS: Fourteen patients with a pouch who had normal pouch emptying and anal function were studied. Ambulatory pouch and anal motility, and stool weights, were recorded for 24 h while taking no medication and for 24 h while receiving 8 mg loperamide. In a second analysis, patients were divided on the basis of bowel frequency into those with 4 or fewer motions (good function; n=6) and those with more than 6 per day (poor function; n=8), to determine any differential effects of loperamide. RESULTS: Loperamide decreased median bowel frequency (no loperamide 5.5 versus loperamide 4.0, P=0.03) and 24-h stool weight (610 g versus 413 g, P=0.03) but not individual stool weights. Patients with poor function had both higher bowel frequency (8.0 versus 3.5 per 24 h, P=0.004) and higher stool weight (728 g versus 430 g, P=0.05) with no treatment than those with good function. High-amplitude pouch pressure waves were greater in number before defaecation in patients with poor function and did not decrease with loperamide, in contrast to patients with good function. Pouch baseline pressure decreased after defaecation to a similar extent in both groups and was not affected by loperamide. CONCLUSION: Loperamide 8 mg per day reduces bowel frequency by reducing total stool weight, not individual stool weights. In patients with good function it also affects pouch motility. High bowel frequency is associated with increased pouch high-pressure waves.

Adenomatous Polyposis Coli↗
PubMed2005

mu-Opiate receptor agonist loperamide blocks bethanechol-induced gallbladder contraction, despite higher cholecystokinin plasma levels in man.

UNLABELLED: mu-Opiate receptor agonists, such as loperamide, influence biliary excretion and suppress cholecystokinin (CCK)-induced gallbladder contraction. Loperamide decreases cholinergic mechanisms, like pancreatic polypeptide (PP) release, while muscarinic agonist (bethanechol)-induced PP release remains unaffected. The effects of loperamide on gallbladder contraction and peptide release were performed to resolve this discrepancy. METHODS: Six subjects (27.6 +/- 2.0 years) received bethanechol (12.5, 25 and 50 microg kg(-1) h(-1) continuously over 40 min) after oral 16 mg loperamide (vs placebo) in a crossover design. Gallbladder volume and plasma levels of CCK, PP, motilin, gastrin, neurotensin, cholylglycine were measured regularly. RESULTS: Bethanechol significantly reduced gallbladder volume (26.7 +/- 1.9 to a nadir of 15.3 +/- 2.2 mL, P < or = 0.05), and this action was inhibited by loperamide. Basal CCK levels increased significantly after loperamide. Incremental integrated CCK release after bethanechol was higher under loperamide (P < or = 0.05), as placebo CCK release was significantly decreased under bethanechol (2.0 +/- 0.4-0.8 +/- 0.3 pmol L(-1)). In both settings, PP levels were significantly increased after bethanechol, while release of neurotensin, motilin, gastrin and cholylglycine was unaffected. CONCLUSION: The mu-opiate receptor agonist loperamide inhibits bethanechol-induced gallbladder contraction. This effect is not mediated by inhibition of CCK release, as loperamide even enhances basal CCK plasma levels. As cholinergic mechanisms, like bethanechol-induced incremental PP release, were unaffected, mu-opiate agonists might influence gallbladder contraction via vagal-cholinergic pathways.

Adult↗
PubMed2005

Loperamide inhibits the biliary excretion of irinotecan (CPT-11) in the rat isolated perfused liver.

Patients treated with irinotecan (CPT-11) occasionally suffer from severe diarrhoea and aggressive treatment with loperamide at the first signs of loose stools is recommended. We have examined the effect of loperamide on the hepatic metabolism and biliary excretion of CPT-11 in the isolated perfused rat liver (IPRL). CPT-11 (0.5 mumol) was injected as a bolus into the IPRL reservoir, and perfusate and bile samples were collected over 3 h. Experiments were conducted using loperamide-free perfusate (n = 5) or perfusate containing 10 muM loperamide (n = 6). Perfusate and bile concentrations of total CPT-11 and the major metabolites SN-38 (7-ethyl-10-hydroxy-camptothecin), SN-38G (7-ethyl-10-hydroxy-camptothecin glucuronide) and APC (7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidine] carbonyloxycamptothecin) were determined by HPLC. The unchanged parent drug was the predominant species in bile, with approximately 4% of the dose recovered over 180 min as compared with only 1% for the metabolites. Loperamide significantly reduced the biliary excretion of CPT-11 by approximately 50% (2.0 +/- 0.9% dose compared with 3.8 +/- 1.0% in the control group, P = 0.019) over the same period. In contrast, the biliary excretion of SN-38, SN-38G and APC was not significantly affected by loperamide (P > 0.05). Furthermore, bile flow rate was not affected by loperamide. Loperamide appeared to selectively inhibit the biliary excretion of CPT-11, although the extent to which loperamide altered the disposition of CPT-11 in the clinical setting remains to be determined.

Animals↗
PubMed2004

Reduction of saquinavir exposure by coadministration of loperamide: a two-way pharmacokinetic interaction.

OBJECTIVE: To assess any pharmacokinetic interactions between loperamide and saquinavir. DESIGN: Double-blind, double-dummy, randomised, placebo-controlled, three-way crossover trial. PARTICIPANTS: Twelve healthy male and female volunteers, aged 24-46 years. METHODS: Saquinavir and loperamide pharmacokinetics were determined over a 72-hour period after single dose administration of saquinavir 600mg and/or loperamide 16mg. Plasma and urine concentrations of loperamide, its metabolites, and saquinavir were analysed using a single liquid chromatography/tandem mass spectrometry method for all compounds. RESULTS: Saquinavir exposure was reduced by 54% when given with loperamide (median area under the concentration-time curve from zero to infinity [range], 1189 [243-2113] vs 550 [234-1468] pmol . h/mL; p = 0.016) with unchanged renal clearance. In contrast, loperamide concentrations increased and desmethylloperamide concentrations decreased during saquinavir coadministration, resulting in a reduced metabolic clearance of loperamide (median [range], 544 [224-1393] vs 443 [238-692] mL/min; p = 0.016). CONCLUSIONS: Whereas the effect of saquinavir on loperamide disposition is unlikely to be of clinical relevance, the reduced drug exposure of saquinavir when loperamide is coadministered is worrisome because a relationship between protease inhibitor drug exposure and antiviral response has been reported. Patients receiving saquinavir monotherapy should be advised not to combine these drugs, especially for prolonged periods of time because a reduction in therapeutic efficacy may result.

Adult↗
PubMed2001

A comparison of the effect of loperamide in oral or suppository form vs placebo in patients with ileo-anal pouches.

OBJECTIVE: The effect of the anti-diarrhoeal drug, loperamide hydrochloride, on bowel function in patients with an ileo-anal pouch was studied by means of a blinded, three-tailed, case-controlled and randomized crossover trial, using a daily dose of 12 mg in either oral (4 mg t.d.s.) or suppository (6 mg b.d.) form. PATIENTS AND METHODS: Daily stool frequency was recorded in a diary and an objective measure of pouch motor function was obtained at the end of each treatment phase. Ten subjects (seven males, three females) aged 23-50 years (median 38 years) were studied 9-48 months (median 27 months) after ileostomy closure. Eight pouches had been constructed for ulcerative colitis and two for familial adenomatous polyposis (9J, 1W). RESULTS: Mean daily stool frequency during the oral loperamide phase was lower than during both the placebo (P=0.05) and suppository (P < 0.02) phases. Stool frequency did not differ significantly between placebo and suppository phases. There was a strong inverse correlation between mean daily stool frequency and pouch capacity (r=-0.82 after both oral and suppository phases). Large isolated pouch contractions were evident in five of eight subjects studied; suppression was observed in two of the five after oral loperamide and in three of the five after loperamide suppositories. Rhythmic pouch contractions were seen in four subjects and suppression was evident after loperamide suppositories (but not after oral loperamide) in three. A daily oral dose of 12 mg loperamide significantly lowered stool frequency in pouch patients and modified some aspects of pouch contraction. Loperamide suppositories produced more prominent suppression of pouch contractions but did not lower stool frequency. CONCLUSION: This suggests that the beneficial effect of oral loperamide is primarily due to its action on intestine proximal to the pouch itself.

Clinical Trial↗
PubMed1997

Inhibition of pancreaticobiliary secretion by loperamide in humans.

Loperamide, a peripherally acting opiate receptor agonist with antidiarrheal action, inhibits ileal and colonic motor function. It was determined whether loperamide also affects gallbladder emptying and pancreatic enzyme secretion in humans. Plasma cholecystokinin (radioimmunoassay), gallbladder volume (ultrasonography), and intraduodenal bilirubin and amylase output (spot sampling) were measured at regular intervals before and during intraduodenal perfusion of an amino acid meal in 8 healthy subjects: once without and once with pretreatment of 8 mg loperamide, ingested 13 and 4 hours before the start of the meal. Loperamide decreased basal amylase output from 3.2 +/- 0.5 to 1.0 +/- 0.5 kU/h (P < .005) and abolished basal bilirubin output (21 +/- 5 vs. 0 +/- 0 micromol/h; P < .005) into the duodenum. Loperamide increased basal gallbladder volume from 28 +/- 4 to 39 +/- 4 mL (P < .0001) but was without effect on basal plasma cholecystokinin (2.7 +/- 0.3 vs. 3.0 +/- 0.3 pmol/L). During the amino acid meal, pretreatment with loperamide inhibited amylase output from 5.1 +/- 0.8 to 1.6 +/- 0.4 kU/h (P < .001), bilirubin output from 39 +/- 6 to 18 +/- 6 micromol/h (P < .0005) and gallbladder contraction from 47% +/- 3% to 26% +/- 6% (P < .05), whereas loperamide enhanced amino acid-stimulated plasma cholecystokinin from 4.5 +/- 1.6 to 7.6 +/- 1.0 pmol/L (P < .05). It is concluded that loperamide inhibits basal and amino acid-stimulated gallbladder motility and intraduodenal output of bilirubin and amylase, despite an enhanced postprandial cholecystokinin release.

Adult↗
PubMed1991

Effect of loperamide on jejunal electrolyte and water transport, prostaglandin E2-induced secretion and intestinal transit time in man.

Jejunal perfusion was performed in 12 healthy volunteers to evaluate the dose dependent effects of loperamide on intestinal absorption, stimulated secretion and transit. In 6 volunteers intestinal perfusion of the jejunal segment with isotonic NaCl solution was followed by addition of loperamide in increasing doses (2-8 mg.l-1). The volunteers were pretreated with 1 mg.l-1 prostaglandin E2 (PgE2) in the perfusate before addition of 4 mg.l-1 loperamide. Phenolsulphonphtalein (PSP) boluses (2 ml) were given to measure mean transit time (MTT). Loperamide 2 mg.l-1 converted the minor secretion after perfusion with the standard solution (water -145 ml.min-1, Na -0.09 and Cl -0.04 mmol.min-1) to absorption (water 0.93 ml.min-1, Na 0.23, Cl 0.25 mmol.min-1) within 15 min. Higher doses of loperamide did not increase absorption. The addition of PgE2 induced net secretion of water (-4.48 ml.min-1) and electrolytes (Na -0.57, Cl -0.51 mmol.min-1). Loperamide 4 mg.l-1 significantly diminished the PgE2-induced net secretion by approximately 50%. Loperamide dose dependently increased the MTT from 6 (2 mg.l-1) to 13.3 min (8 mg.l-1). MTT was still delayed 60 min after a wash out period (10.5 min). It is concluded that loperamide had a dual effect or intestinal activities stimulating absorption and prolonging intestinal transit time with rising doses.

Adolescent↗
PubMed1993

Loperamide abolishes exercise-induced orocecal liquid transit acceleration.

Previous work in our laboratory has found that mild physical activity accelerates mouth-to-large intestinal transit of lactulose in a mixed liquid meal. Because loperamide is commonly used as an antidiarrheal agent, we wondered if it would blunt the orocecal transit acceleration provoked by mild exercise. We investigated this equation in 12 healthy persons by comparing orocolonic liquid transit at rest and in mild exercise. Each subject ingested 8 mg loperamide 1 hr prior to study under both resting and exercise conditions. With loperamide treatment, exercise (walking at 5.6 km/hr) failed to hasten increased H2 excretion (mean transit time 72 +/- 12 min at rest, 90 +/- 15 min in exercise; P = NS). This result contrasts sharply with previously reported controls: loperamide completely abolished exercise-induced orocecal transit acceleration (-23 +/- 5 min in controls; +18 +/- 13 min with loperamide; P < 0.05). Compared with these same controls, resting transit was not significantly slowed by the drug, while transit in exercise was retarded (64 +/- 5 min in controls, 90 +/- 15 min with loperamide; P = 0.06). Loperamide left unchanged the heart rate and oxygen uptake rises associated with exercise. In summary, by showing that loperamide blocks an exercise effect on the upper gut, these results suggest that the drug might prove effective in treating some gut symptoms induced by physical activity.

Adult↗
PubMed1984

Loperamide-induced inhibition of pancreatic secretion in rats.

The effects of loperamide on exocrine pancreatic secretion were studied in rats fitted with chronic or acute fistulas. Intraduodenal injection of loperamide in conscious rats resulted in a dose-dependent inhibition of basal pancreatic secretion involving volume and bicarbonate and protein output with an ED50 of about 0.5 mg/kg. The maximal inhibition observed was about 60% for volume and bicarbonate output and 90% for protein output. Loperamide induced an inhibition of pancreatic secretion in conscious rats that was naloxone-sensitive and persisted in cimetidine-treated rats. Thus, it did not depend on modifications of gastric secretion. In anaesthetized rats, loperamide did not inhibit the pancreatic secretion evoked by agents acting directly on the pancreatic cells (acetylcholine, secretin, CCK) but it inhibited by 100% the pancreatic secretion induced by vagal electrical stimulation (VES) and by 80-100% that induced by 5 thio-glucose, a centrally acting vagal stimulatory agent. Loperamide inhibition of VES-induced pancreatic secretion was different from that obtained with morphine or methadone since these opiate drugs could only inhibit by 50-60% maximally the VES-stimulated pancreatic secretion. The loperamide inhibition of VES-induced secretion was naloxone-insensitive, while loperamide inhibition of 5 thio-glucose-induced secretion was in part naloxone-sensitive. These results suggest that loperamide exerts a potent inhibition of pancreatic secretion by acting on the nerve supply to the pancreas through both opiate and non-opiate mechanisms.

Acetylcholine↗
PubMed2003

Development of tolerance to the inhibitory effect of loperamide on gastrointestinal transit in mice.

The inhibitory effect of repetitiously administered loperamide, a peripheral mu-opioid receptor agonist and well-recognized antidiarrheal agent, on mouse gastrointestinal transit was compared with that of morphine in order to examine the development of tolerance to mu-opioid receptor agonist-induced constipation (antitransit effect). When administered subcutaneously 15 min before the oral injection of charcoal meal, loperamide (0.1-30 mg/kg) and morphine (1-8 mg/kg) dose-dependently and significantly inhibited gastrointestinal transit of charcoal with the ID(50) values of 1.6 (0.3-7.1) mg/kg and 3.6 (1.5-8.5) mg/kg, respectively. When loperamide (30 mg/kg) was administered twice daily for 2 days, the antitransit effect was significantly reduced. On the other hand, morphine did not develop tolerance in even more severe conditions than those of loperamide. It is known that P-glycoprotein, an ATP-dependent drug efflux pump, is involved in the development of tolerance to morphine analgesia. The tolerance observed with loperamide was significantly prevented by cyclosporin (30 mg/kg, i.p.), a P-glycoprotein inhibitor, thus the ID(50) value in loperamide-tolerant mice was markedly reduced from >1000 mg/kg to 40 (2.7-603.0) mg/kg by cyclosporin. These results indicate that loperamide, different from morphine, readily develops tolerance to the inhibitory effect on mouse gastrointestinal transit, and the P-glycoprotein may be involved in the development of tolerance to the antitransit effect of loperamide.

Animals↗
PubMed2003

No effect of MDR1 C3435T variant on loperamide disposition and central nervous system effects.

BACKGROUND: The MDR1 gene encodes the efflux transporter P-glycoprotein, which is highly expressed in the small intestine and in the blood-brain barrier. A major function of P-glycoprotein is to limit the absorption and central nervous system exposure of numerous xenobiotics. A genetic polymorphism in the MDR1 gene (C3435T) has been associated with changes in the intestinal expression level and function of P-glycoprotein. The aim of this study was to investigate the effect of this polymorphism on disposition and brain entry of the P-glycoprotein substrate loperamide. METHODS: Healthy white volunteers were genotyped for the MDR1 C3435T polymorphism, and a 16-mg oral dose of loperamide was administered to 8 subjects with the 3435TT genotype and 8 subjects with the 3435CC genotype. Plasma levels of loperamide were determined by liquid chromatography-tandem mass spectrometry. Loperamide-induced respiratory depression was detected as the ventilatory response to carbon dioxide and was used as a measure of central nervous system side effects. RESULTS: We found no significant difference in loperamide pharmacokinetics between individuals homozygous for the C and the T alleles in position 3435 of MDR1, as follows: peak plasma drug concentration, 3164 +/- 1053 pg/mL and 3021 +/- 984 pg/mL; area under the concentration-time curve from 0 to 8 hours, 14414 +/- 4756 pg. h/mL and 14923 +/- 6466 pg. h/mL; and time to peak plasma drug concentration, 3.9 +/- 1.4 hours and 3.9 +/- 2.6 hours for the MDR1 3435CC and 3435TT genotypes, respectively (P >.05, for all parameters). Hypercapnic ventilatory response changed only minimally after ingestion of loperamide (the coefficient of variation during the 0- to 8-hour period was 21% +/- 14% for the sample population), and there was no MDR1 3435 genotype-related effect on respiratory response. Carriers of the 2 major MDR1 haplotypes, MDR1*1 and MDR1*13, did not differ in their response to loperamide. CONCLUSION: There was no association between the MDR1 C3435T variation and plasma levels or central nervous system effects of the P-glycoprotein substrate loperamide in a white study population. The MDR1 haplotype structure was quite variable and supports the use of haplotypes instead of single nucleotide polymorphisms in determining clinical consequences of genetic variation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Comparison of racecadotril and loperamide in children with acute diarrhoea.

METHODS: A multicentre, parallel-group, double-blind, double-placebo study was carried out to compare the efficacy, tolerability, and safety of racecadotril and loperamide in children aged 2 to 10 years who were suffering from acute diarrhoea. Patients received racecadotril (1.5 mg/kg) or loperamide (0.03 mg/kg) three times daily plus matching placebo until recovery. Fifty-two children received racecadotril and 50 loperamide. RESULTS: Patients on racecadotril passed a mean (+/- S.E.M.) of 2.7 +/- 0.4 stools before recovery compared with 2.1 +/- 0.4 stools for loperamide. The duration of diarrhoea was similar with both treatments. The incidence of adverse events was lower with racecadotril than with loperamide (11.5% vs. 22%), and significantly more patients on loperamide suffered from constipation (58% vs. 36.5%; P = 0.03). Moreover, significantly more children receiving loperamide required concomitant medication during the study (38% v 19.2%; P = 0.047). Measurement of abdominal circumference at the final consultation, 6 days after entry to the study, revealed no significant differences between treatments. CONCLUSIONS: Racecadotril and loperamide were equally effective in treating acute diarrhoea in these children, and racecadotril had a superior tolerability and safety profile.

Acute Disease↗
PubMed1997

Loperamide: a positive modulator for store-operated calcium channels?

The depletion of inositol trisphosphate-sensitive intracellular pools of calcium causes activation of store-operated calcium (SOC) channels. Loperamide at 10-30 microM has no effect on intracellular calcium levels alone, but augments calcium levels in cultured cells when SOC channels have been activated. In HL-60 leukemic cells, the apparent positive modulatory effect of loperamide on SOC channels occurs when these channels have been activated after ATP, thapsigargin, or ionomycin-elicited depletion of calcium from intracellular storage sites. Loperamide has no effect when levels of intracellular calcium are elevated through a mechanism not involving SOC channels by using sphingosine. Loperamide caused augmentation of intracellular calcium levels after activation of SOC channels in NIH 3T3 fibroblasts, astrocytoma 1321N cells, smooth muscle DDT-MF2 cells, RBL-2H3 mast cells, and pituitary GH4C1 cells. Only in astrocytoma cells did loperamide cause an elevation in intracellular calcium in the absence of activation of SOC channels. The augmentation of intracellular calcium elicited by loperamide in cultured cells was dependent on extracellular calcium and was somewhat resistant to agents (SKF 96365, miconazole, clotrimazole, nitrendipine, and trifluoperazine) that in the absence of loperamide effectively blocked SOC channels. It appears that loperamide augments influx of calcium through activated SOC channels.

3T3 Cells↗
PubMed1993

Loperamide inhibits corticotrophic cell function by a naloxone-insensitive mechanism in the rat in vitro.

The effect of the antidiarrheal drug loperamide, a mu-opiate agonist, on ACTH secretion and biosynthesis, cAMP generation and phosphoinositide turnover was studied in rat anterior pituitary cell cultures. The cAMP-dependent protein kinase A pathway was stimulated with both corticotropin-releasing hormone (CRH; 2-5 nM) and the membrane-permeable Bu(2)cAMP (0.5-2.5 mM). The protein kinase C pathway was stimulated with 1 microM arginine vasopressin (AVP) and 1-10 nM phorbol 12-myristate 13-acetate (PMA). After 3.5 h, loperamide (10 microM) had no effect on basal ACTH levels but significantly suppressed CRH-induced ACTH release, in a dose-dependent manner, to 60 +/- 4% of control (100%) (p < 0.0001). After 24 h, basal proopiomelanocortin mRNA was significantly decreased to 50% of control by loperamide (p < 0.05). The suppressive effect of loperamide on CRH-induced ACTH secretion was not reversible by naloxone (0.1-1,000 microM). Morphine (0.01-10 microM) had no effect on basal and CRH-induced ACTH secretion. Loperamide did not influence basal and CRH-induced adenylate cyclase activity in anterior pituitary cell membrane preparations, but it significantly blunted Bu(2)cAMP-induced ACTH secretion in cell culture from 100 +/- 4 to 77 +/- 4% (p < 0.05). In Ca(2+)-depleted medium (Ca2+ < 0.1 mM), loperamide had no suppressive effect on CRH-induced ACTH secretion. AVP-induced ACTH secretion was significantly suppressed by loperamide from 100 +/- 5 to 74 +/- 3% (p < 0.0001), while basal and AVP-induced inositol 1-phosphate generation and PMA-induced ACTH secretion were not affected by loperamide.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1999

A multicenter randomized controlled trial of a liquid loperamide product versus placebo in the treatment of acute diarrhea in children.

This randomized, double-blind, placebo-controlled trial of 48 hours' duration conducted in 13 primary care ambulatory practices in the United States and Mexico was used to compare the efficacy and safety of loperamide with placebo for the treatment of acute diarrhea in children aged 2 through 11 years. Two hundred fifty-eight children with acute nonspecific diarrhea were enrolled. Children were randomly assigned to treatment with loperamide HCl 0.5 mg/5 mL (n = 130) or placebo (n = 128). The first dose of loperamide consisted of either 1.0 mg (children 2 through 5 years of age) or 2.0 mg (children 6 through 11 years of age) of study medication under the observation of study personnel. This was followed by 1 mg after each unformed stool, with a total daily dose of up to 3.0 mg in the children 2-5 years of age, 4.0 mg in the children 6-8 years of age, and 6.0 mg in the children 9-11 years of age. The primary outcome measures were time to last unformed stool, time to first unformed stool, number of unformed stools during six consecutive 8-hour periods, and overall rating of efficacy/acceptability. Secondary outcomes included abdominal pain/cramping, vomiting, and fever. Children who received loperamide had significantly shorter time to last unformed stool (p = 0.0017) and fewer numbers of unformed stools (p = 0.0237) than children who received placebo. The end-of-study overall efficacy/acceptability rating of loperamide was significantly better than for placebo (p = 0.0107). All other clinically important outcome measures related to diarrhea relief favored loperamide. There was no significant difference in the incidence of drug-related adverse events between treatment groups, although total adverse events were reported more frequently (p = 0.048) by the loperamide group (15%) compared with the placebo group (7%). In conclusion, this controlled study provides data demonstrating that at recommend doses, loperamide is well tolerated and significantly shortens the duration and severity of symptoms of acute nonspecific diarrhea in children 2 through 11 years of age.

Acute Disease↗
PubMedDate not supplied

Loperamide oxide for the treatment of chronic diarrhoea in Crohn's disease.

Loperamide oxide was compared with placebo for the treatment of chronic diarrhoea in patients with Crohn's disease. After initially receiving 2 mg loperamide oxide or placebo, hospital out-patients with Crohn's disease were instructed to take one tablet of loperamide oxide (1 mg) or placebo after passage of each unformed stool in a 1-week double-blind investigation. Patients who responded to this treatment by passing less than three unformed stools per 24 h continued to receive the drug, twice daily, for a further week. At the end of the initial 1-week treatment phase both the investigator's and the patients' global evaluations of efficacy were significantly in favour of the active treatment (P = 0.025 and P = 0.020, respectively). The investigator's assessment of the change in abdominal pain was significant for loperamide oxide (P = 0.020) but not for placebo. Improvements in patient-rated severity of diarrhoea were significantly greater for loperamide oxide than for placebo (P = 0.046). The mean daily dose of loperamide oxide was 2.7 mg. During the second week, both the investigator's and the patients' assessments of global efficacy and symptom improvement continued to favour loperamide oxide though the differences were not significant. Adverse events were rare. The results suggest that loperamide oxide (3 mg/per day) provides a safe and effective treatment for the chronic diarrhoea associated with Crohn's disease.

Adolescent↗
PubMed2000

Effect of loperamide on Na+/D-glucose cotransporter activity in mouse small intestine.

The mu-opioid agonist loperamide is an antidiarrhoeal drug which inhibits intestinal motility and secretion. Its anti-absorptive effects are less well investigated, but may be mediated through calmodulin. We have investigated further the effect of loperamide on the intestinal Na+-dependent D-glucose transporter (SGLT1). Brush-border membrane vesicles were prepared from mouse small intestine, and uptake of [3H]glucose was measured. Na+-dependent glucose uptake displayed the typical overshoot at 34 s; the peak value was 1.6 nmol mg(-1). The overshoot disappeared in the presence of phlorizin or when Na+ was replaced by K+. Extravesicular loperamide dose-dependently inhibited SGLT1 activity with an IC50 value of 450 micromol L(-1). Loperamide displayed a mixed inhibition type: the apparent Vmax decreased from 0.9 to 0.5 nmol mg(-1)/15 s, the apparent Km increased from 0.23 to 1.13 mmol L(-1) glucose. Na+ kinetics were more complex, but loperamide inhibited net glucose uptake by 90% at 100 mmol L(-1) Na+. Glucose uptake was unchanged by agents affecting calmodulin activity. Loperamide inhibited intestinal Na+, K+-ATPase activity, whilst sucrase activity was unaffected. SGLT1 activity was inhibited by loperamide, but this effect was not mediated through calmodulin. As this action is only evident at high concentrations of loperamide a nonspecific mechanism may be involved.

Animals↗
PubMed1994

Effect of loperamide on lower oesophageal sphincter pressure in idiopathic achalasia.

BACKGROUND: We have recently shown that in achalasia patients morphine has a striking inhibitory action on resting lower oesophageal sphincter (LOS) pressure, which is mediated by opioid receptors. The aim of this study was to investigate the effect of a peripheral opioid agonist, loperamide, administered at a dose of 16 mg, on resting LOS pressure in nine patients with untreated idiopathic achalasia. METHODS: All patients underwent two experiments after oral administration of placebo and loperamide, respectively, on separate days and in randomized order. At the end of the placebo experiment we also tested the effect of loperamide as compared with distilled water, both infused intraluminally at the level of the LOS. In the loperamide experiment, after a 60-min basal period, naloxone, 40 micrograms/kg, was injected intravenously, and recordings continued for a further 10 min. RESULTS: Loperamide administered orally decreased (p < 0.01) LOS pressure by 10 +/- 2 mmHg (37 +/- 7%) compared with placebo, and naloxone intravenously failed to block the effect. LOS pressure was not affected by infusion of either distilled water or loperamide at the level of the LOS. CONCLUSIONS: Our findings indicate that in patients with idiopathic achalasia oral administration of loperamide at a high dose markedly decreases resting LOS pressure. This may not occur through opioid receptor stimulation and requires intestinal absorption of the drug. The possible effect of combining a small dose of loperamide with the traditional achalasia drugs awaits further evaluation.

Administration, Oral↗