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PubMed1997

A randomized double blind placebo controlled multicenter study of mesalazine for the prevention of acute radiation enteritis.

BACKGROUND AND PURPOSE: Symptoms of acute radiation enteritis (ARE), dominated by diarrhea, occur in more than 70% of patients receiving pelvic irradiation. Eicosanoids and free radicals release have been implicated in the pathogenesis. Mesalazine (5-ASA) is a potent inhibitor of their synthesis in the mucosa and could therefore be of some interest in preventing ARE. PATIENTS AND METHODS: The study was performed in six radiotherapy units in France who agreed on standardized irradiation procedures. One hundred and fifty-three patients planned for external beam radiotherapy to the pelvis > or = 45 Gy for prostate (n = 97) or uterus (n = 54) cancer were randomized on a double blind basis to receive prophylactic 5-ASA (4 g/day Pentasa) or placebo. Patients with concomitant chemotherapy were excluded. Prostate and uterus cancers were chosen since these centropelvic tumors require a similar radiotherapy protocol during the first step of treatment and involve a comparable volume of small intestine. The symptoms of ARE and their severity were assessed every week during irradiation, and 1 and 3 months after its end. All patients followed a low fiber and low lactose diet. End points were diarrhea, use of antidiarrheal agents, abdominal pain, and body weight. Effficacy was evaluated using intention to treat. RESULTS: (means +/- SD) Groups did not differ for age (mean 64 +/- 9 years), sex, tumor site, or irradiation procedure. During irradiation, diarrhea occurred in 69% and 66% of the 5-ASA and placebo groups, respectively (chi2, P = 0.22). Curves of survival without diarrhea did not differ between groups (logrank P = 0.09). Severity of diarrhea did not differ between groups except at d15 where it was significantly more severe in the 5-ASA group (ANOVA P = 0.006). Duration of diarrhea did not differ (22 +/- 15 days in both groups, P = 0.88). Abdominal pain was less frequently reported in the 5-ASA group at d28 (34% vs. 51%, P = 0.048). Use of antidiarrheal agents and body weight did not differ between groups. CONCLUSION: Mesalazine 4 g/day did not decrease the symptoms of ARE.

Acute Disease↗
PubMed2000

Discrepancies between effects of recombinant human growth hormone on absorption and secretion of water and electrolytes on the human jejunum compared to results reported on rat jejunum.

Previous studies in rats showed that the administration of recombinant human growth hormone markedly increased intestinal absorption of electrolytes and water and suggested that growth hormone would be a useful antidiarrheal agent. We therefore examined the effect of recombinant human growth hormone on the human jejunum in vivo, using a triple lumen nonabsorbable marker technique. Healthy subjects were studied on two different test days, one as a control and a second where recombinant human growth hormone was injected subcutaneously in a dose of 100 microg/kg. With this dose we achieved equal or higher growth hormone serum levels than in previous rat studies. However the administration of recombinant human growth hormone did not stimulate absorption or inhibit secretion of water and electrolytes in the human jejunum in vivo. We believe that the discrepancy between humans and rats is most likely due to the species difference rather than to differences in methods that were used. Therefore recombinant human growth hormone cannot be considered a useful proabsorptive antidiarrheal agent in humans.

Adult↗
PubMed2002

Effects of seirogan (wood creosote) on propulsive colonic motility and stool characteristics in ambulatory mini-pigs.

Our goal was to determine whether Seirogan, an herbal medicine used as an antidiarrheal agent, modifies colonic function, including motility. Experiments were performed on four female Yucatan mini-pigs with established permanent cecal fistulas providing direct access to the colon. Long-term recordings of proximal colonic motility were accomplished by a solid-state probe (six pressure ports 10 cm apart), and a motility index was calculated. Stool viscosity was also measured. The laxative bisacodyl (15 mg/kg) was used to induce colonic motility (increase in motility index) and stool softening, prior to investigating the effect of Seirogan (2-15 mg/kg per os twice a day) or a vehicle control. Seirogan (15 mg/kg), but not the placebo, reversed the bisacodyl-induced stool softening and restored the motility index to normal values by reducing the number of propagating contractions. Taken together the results suggest that inhibition of proximal colonic motility by Seirogan may contribute to its antidiarrheal action.

Animals↗
PubMed1981

Salicylate absorption from a bismuth subsalicylate preparation.

The active ingredient in Pepto-Bismol (PB) (Norwich-Eaton), a common antidiarrheal, is bismuth subsalicylate. The absorption of salicylate after oral PB was studied in six fasted men. Plasma concentrations of total salicylate and the urinary excretion profile of salicylate were determined as a function of time and dose. After 60 ml PB, 500.1 +/- 33.6 mg (mean +/- SD) salicylate were recovered in urine, representing 95.0 +/- 6.4% of salicylic acid equivalents in 60 ml of the formulation. Peak plasma salicylate levels were reached 0.5 to 3 hr after ingestion and averaged 40.1 +/- 17.3 micrograms/ml. Absorption of salicylate was also essentially complete after 15- and 30-ml doses of the antidiarrheal preparation, and a linear relationship between dose and recovery of salicylate in the urine was found. Salicylate kinetics was nonlinear after a multiple-dose regimen of 60 ml every 6 hr for five doses.

Adult↗
PubMed2004

Prolonged diarrhea due to ciprofloxacin-resistant campylobacter infection.

BACKGROUND: Campylobacter causes >1 million infections annually in the United States. Fluoroquinolones (e.g., ciprofloxacin) are used to treat Campylobacter infections in adults. Although human infections with ciprofloxacin-resistant Campylobacter have become increasingly common, the human health consequences of such infections are not well described. METHODS: A case-control study of persons with sporadic Campylobacter infection was conducted within 7 FoodNet sites during 1998-1999. The E-test system (AB Biodisk) was used to test for antimicrobial susceptibility to ciprofloxacin; ciprofloxacin resistance was defined as a ciprofloxacin minimum inhibitory concentration of > or =4 microg/mL. We conducted a case-comparison study of interviewed persons who had an isolate tested. RESULTS: Of 858 isolates tested, 94 (11%) were ciprofloxacin resistant. Among 290 persons with Campylobacter infection who did not take antidiarrheal medications, persons with ciprofloxacin-resistant infection had a longer mean duration of diarrhea than did persons with ciprofloxacin-susceptible infection (9 vs. 7 days [P=.04]). This difference was even more pronounced among the 63 persons who did not take antidiarrheal medications or antimicrobial agents (12 vs. 6 days [P=.04]). In a multivariable analysis-of-variance model, the persons with ciprofloxacin-resistant infection had a longer mean duration of diarrhea than did the persons with ciprofloxacin-susceptible infection (P=.01); this effect was independent of foreign travel. The association between ciprofloxacin resistance and prolonged diarrhea is consistent across a variety of analytical approaches. CONCLUSIONS: Persons with ciprofloxacin-resistant Campylobacter infection have a longer duration of diarrhea than do persons with ciprofloxacin-susceptible Campylobacter infection. Additional efforts are needed to preserve the efficacy of fluoroquinolones.

Adolescent↗
PubMed1996

Influence of location and staff knowledge on quality of retail pharmacy prescribing for childhood diarrhea in Kenya.

BACKGROUND: Retail pharmacies are important sources of advice on pharmaceuticals in developing countries, where many purchasing decisions are unmediated by medical professionals. For childhood diarrhea, choice of drug sales in pharmacies has been found to be consistently poor, whether with or without prescription, as evidenced by a low use of effective oral rehydration salts (ORS) and high use of marginally effective or ineffective products such as antimotility agents, adsorbents, and antimicrobials. Little information is available about factors influencing prescribing by pharmacy personnel in these settings. This paper reports results of an analysis which examined the influence of rural versus urban location, neighborhood socio-economic status (SES), and clinical knowledge of pharmacy assistants on quality of prescribing in retail pharmacies in Kenya. METHODS: Using WHO treatment guidelines, we measured quality of prescribing in childhood diarrhea as: (1) the proportion of client encounters in which ORS is prescribed (indicating higher quality practice); and (2) the proportion of visits in which an antidiarrheal product is prescribed (lower quality practice). We obtained data on prescribing in a simple case of childhood diarrhea using surrogate patient visits to 91 pharmacies located in the major urban area of Kenya (Nairobi) and four rural towns. Multivariate logistic regression was used to examine the association between pharmacy predictor variables and the quality of prescribing. RESULTS: No consistent relationship was found between the clinical knowledge of pharmacy assistants and quality of prescribing. Controlling for number of products prescribed, gender of the assessor, and level of knowledge, multivariate analyses indicated that in comparison to rural pharmacies, the odds of prescribing ORS were significantly higher in pharmacies located in high SES (OR = 4.7; 95% CI = 1.4,16.1) or middle SES (OR = 4.5; CI = 1.9,10.6) urban neighborhoods; the odds in low SES urban pharmacies were similar to those in rural areas (OR = 2.0; CI = 0.6,6.2). The odds of prescribing antidiarrheal products did not differ significantly in any geographic area. CONCLUSIONS: Location of a retail pharmacy in a rural area or in a low-income urban neighborhood was associated with suboptimal quality of prescribing as evidenced by lower use of ORS. No relationship between clinical knowledge and quality of practice was detected. Future research is needed to examine such factors as the influence of intra-pharmacy authority structure, perceived efficacy of pharmaceuticals, local patterns of physician practice, and economic incentives on the quality of prescribing.

Adult↗
PubMed1993

Subcutaneous octreotide versus oral loperamide in the treatment of diarrhea following chemotherapy.

Forty patients with chemotherapy-related diarrhea were randomized to receive (i) octreotide 0.5 mg three times per day s.c. or (ii) loperamide 4 mg three times per day p.o. until complete remission of diarrhea was achieved. In the octreotide group 80% of patients showed complete resolution of loose bowel movements within 4 days of therapy, while in the loperamide group this goal was obtained in only 30% of cases (p < 0.001). If after 4 days no benefit was seen, patients were considered to have failed antidiarrheal therapy. Failure was recorded in only one case (5%) treated with s.c. octreotide and in five patients (25%) who received loperamide. The mean duration of antidiarrheal therapy necessary to achieve remission was 3.4 days in the octreotide group and 6.1 days in the loperamide group (p < 0.001). Treatment with octreotide was very well tolerated with mild abdominal pain in 15% of cases and pain in the injection site in 15% of patients. Subcutaneous octreotide is highly effective in the management of chemotherapy-related diarrhea in cancer patients.

Administration, Oral↗
PubMed1996

Irinotecan is an active agent in untreated patients with metastatic colorectal cancer.

PURPOSE: To determine the response rate, survival, and toxicity of the new anticancer agent, irinotecan (CPT-11), in the treatment of metastatic colorectal cancer. PATIENTS AND METHODS: Forty-one chemotherapy-naive patients with measurable metastatic colorectal cancer were treated with a 90-minute infusion of irinotecan 125 mg/m2 administered weekly for 4 weeks every 6 weeks. Pretreatment tumor biopsies to assess topoisomerase-I (Topo-I) activity were obtained from 11 patients. The pharmacokinetics for irinotecan and its active metabolite, SN-38, were determined in 18 patients. RESULTS: Thirteen of 41 patients (32%) had a partial response (PR; 95% confidence interval, 18% to 46%). The median response duration was 8.1 months (range, 4.0 to 16.0) and the median survival time was 12.1 months (range, 2.1 to 21.7) for all 41 patients. Grade 3 or 4 toxicities were diarrhea (29% of patients) and neutropenia (22% of patients). Grade 3 or 4 diarrhea was substantially more prevalent in the initial 18 patients on study, with an incidence rate of 56%; a significant reduction in the incidence of severe diarrhea to 9% was noted with strict adherence to an antidiarrheal regimen of loperamide and diphenyldramine. No correlations were seen between pharmacokinetics of irinotecan/SN-38 and the clinical parameters of response, survival, or incidence of diarrhea. CONCLUSIONS: Irinotecan has activity in the treatment of patients with metastatic colorectal cancer. Strict adherence to an antidiarrheal regimen of diphenhydramine/loperamide significantly reduced the incidence of diarrhea; the agent was thereafter well tolerated in the majority of patients.

Adult↗
PubMed2004

Wood creosote inhibits calcium mobilization in Guinea pig colonic smooth muscle.

Wood creosote, a mixture of simple phenolic compounds, has long been used as an herbal antidiarrheal medicine. Previous studies have shown that wood creosote has antimotility activity on the gastrointestinal (GI) tract, although its mechanism of action is not completely understood. The in vitro efficacy of wood creosote on calcium mobilization in guinea pig colonic smooth muscle was evaluated using a digital video camera system mounted on an inverted fluorescence microscope. The effects of wood creosote on spontaneous periodic increases in the free cytosolic calcium concentration ([Ca(2+)](i)), acetylcholine (ACh)-enhanced periodic increases in [Ca(2+)](i), and tetrodotoxin- or nifedipine-resistant spontaneous periodic increases in [Ca(2+)](i) were evaluated. Wood creosote decreased the amplitude of spontaneous (IC(50)=21 microg/ml) and ACh-enhanced (IC(50)=40 microg/ml) periodic increases in [Ca(2+)](i) in guinea pig colonic smooth muscle. Wood creosote also decreased the amplitude of both tetrodotoxin- and nifedipine-resistant spontaneous periodic increases in [Ca(2+)](i). These results suggest that antimotility activity through inhibition of Ca(2+) mobilization in the GI tract is at least partially responsible for the antidiarrheal activity of wood creosote. Wood creosote may exert its antimotility effect, at least in part, on network regions of interstitial cells of Cajal, which act as pacemaker cells and mediators of neurotransmission in the GI tract.

Animals↗
PubMedDate not supplied

[Evaluating the potential of an intervention aimed at promoting oral rehydration therapy (ORT) by educating pharmacy employees].

Diarrhea is a major cause of morbidity and mortality in childhood, and Brazilians rely heavily on pharmacies for the resolution of this and other health problems. To promote the rational use of both pharmaceuticals and oral rehydration therapy (ORT), an intervention study was performed in pharmacies in Southwestern Brazil. Semi-structured interviews showed oral rehydration solution, or ORS (50%), antidiarrheals (39%), trimethoprim-sulfamethoxazole (27%), and yeast (22%) to be the most frequently suggested drugs, whereas questionnaire responses were ORS (75%), trimethoprim-sulfamethoxazole (25%), and yeast (25%), thus revealing that more than one methodology is needed if reliable data are to be obtained. An educational intervention was applied to 86.7% of pharmacies, but acquisition of knowledge on management of diarrhea did not prevent pharmacy workers from suggesting antidiarrheal drugs instead of ORS alone. In order to have pharmacy workers comply with official protocols for episodes of diarrhea, interventions should include regulatory measures on drugs that are contraindicated for children, and the role of pharmacies and pharmacists should be reviewed.

Child, Preschool↗
PubMed2000

Binding of alkyl- and alkoxy-substituted simple phenolic compounds to human serum proteins.

Wood creosote, primarily a mixture of simple alkyl- and/or alkoxy-substituted phenolic compounds with closely related structures, has long been used as an oral antidiarrheal agent. The use of wood creosote as a parenteral antidiarrheal agent was investigated, and for basic pharmacokinetic data we measured the extent of equilibrium binding of its six major constituent phenolic compounds to human serum proteins using an ultrafiltration method. The percent binding of these major constituent phenolic compounds, namely phenol, guaiacol, p-cresol, o-cresol, creosol and 4-ethylguaiacol, bound to 40-mg/ml human serum albumin was 15.5+/-0.9, 28.0+/-1.5, 37.2+/-0.7, 52.3+/-5.3, 36.8+/-2.0 and 56.7+/-2.4%, respectively, while percent binding to human serum (68 mg protein/ml) was 41.3+/-0.7, 42.6+/-0.5, 64.8+/-0.4, 70.1+/-1.6, 65.7+/-0.2 and 83.1+/-0.1% (mean +/- standard deviation, n = 4), respectively, when tested individually at a concentration of 500 micromol/l. Saturation of binding was not observed for the phenolic compounds up to a concentration of 50 mmol/l. Phenolic compounds with a lipophilic substituent showed higher percent binding to proteins than those without it. We conclude that simple phenolic compounds having alkyl- and/or alkoxy-substituents bind to serum proteins to a considerable extent and that the binding is hydrophobic and nonspecific.

Blood Proteins↗
PubMedDate not supplied

Clinico-pathological follow-up after total colectomy and straight ileo-anal anastomosis done for ulcerative colitis.

BACKGROUND: Restorative proctocolectomy is used as surgical treatment for ulcerative colitis. We have earlier documented adaptative changes in the terminal ileum after total colectomy, and straight ileo-anal anastomosis. AIM: To correlate the morphologic and functional changes in the ileal mucosa after total colectomy and hand-sewn straight ileo-anal anastomosis for ulcerative colitis. METHODS: Thirty consecutive patients (age range 15-50 years, 24 men) who had undergone total colectomy, rectal mucosectomy and hand-sewn straight ileo-anal anastomosis for ulcerative colitis were included in the study. These patients were followed up at 3-monthly intervals following surgery for two years and later once every year for a median duration of 9.5 (range 1-17) years. The clinical parameters studied were weight gain, frequency of stools, nature of stools, nocturnal stool frequency and need for antidiarrheal drugs. At each follow-up visit they were subjected to per rectal ileoscopy with ileal biopsy and barium enema. Ileal biopsy was analyzed histologically and histochemically. RESULTS: The clinical features improved over time, with average weight gain of 5 (range 1-7) Kg at one year. Frequency of stools decreased from 8-10 per day to 2-3 per day. The stools became semisolid and there was no need for antidiarrheal drug by the end of one year. All the patients showed adaptative changes in the ileum. The ileal mucosa was completely transformed into colonic type by the end of one year, colonoscopically (spacious lumen characteristic of colon), radiologically (disappearance of ileal characteristics with rectosigmoid-like appearance), histologically (blunting of villi with increase in goblet cells), and histochemically (sialomucin pattern to sulfomucin pattern). CONCLUSIONS: The ileum undergoes adaptative changes with corresponding improvement of clinical parameters over time, after proctocolectomy and ileoanal anastomosis for ulcerative colitis.

Adult↗
PubMed1992

D-xylose malabsorption: characteristic finding in patients with the AIDS wasting syndrome and chronic diarrhea.

The AIDS wasting syndrome (AWS) is characterized by > 10% loss of baseline body weight during 6 months and may occur in patients with or without associated chronic diarrhea. To determine whether the presence of small-intestinal malabsorption is associated with the development of AWS in human immunodeficiency virus (HIV)-infected patients with chronic diarrhea, we retrospectively reviewed the results of D-xylose testing performed in the clinical evaluation of 21 consecutive HIV-infected patients with chronic diarrhea. A thorough search for small-intestinal pathogens was performed including upper endoscopy, duodenal biopsy, and aspirate for culture and ova and parasite examination. These studies were negative in all patients except two who were excluded from the study. In the 19 patients with no identifiable pathogens, the 1-h serum D-xylose concentration was significantly lower in patients with AWS than in those without, 8.3 +/- 0.8 versus 23.7 +/- 3.4 mg/dl, respectively, p < 0.001. Urine D-xylose excretion during 5 h was also significantly lower in the group with AWS, although creatinine clearance was similar in the two groups. Patients with AWS were more often refractory to standard antidiarrheal therapy with loperamide or diphenoxylate and carried a poor prognosis (90% mortality at 1 year versus 22% mortality in the group without AWS). These data indicate that small intestinal malabsorption is a major component in the severe wasting seen in some HIV-infected patients with chronic diarrhea. Patients with markedly abnormal D-xylose tests may require more potent antidiarrheal therapy and are expected to have a high mortality as a possible consequence of intestinal dysfunction.

Acquired Immunodeficiency Syndrome↗
PubMed2000

ADL-2-1294 (Adolor).

Adolor is developing various local and topical formulations of the antidiarrheal compound loperamide (ADL-2-1294), which acts as an opiate receptor agonist in the peripheral nervous system, for the potential treatment of pruritus and pain associated with burns, wounds, eye diseases and inflammation. Both the topical formulation and ophthalmic formulation are in phase II clinical trials. TOPICAL FORMULATION: A topical formulation is being developed for pain associated with cutaneous inflammatory lesions and other indications associated with inflammatory pain. Phase I trials were completed in spring 1997. The trials assessed the safety, tolerance, pharmacokinetics, and topical sensitivity of ADL-2-1294 in 35 burn patient volunteers. Following positive results, Adolor began two dose-ranging phase II trials in patients with minor burns, abrasions and sunburn in the first half of 1997. In July 1997, Adolor was to initiate the preclinical development of ADL-2-1294 for the potential treatment of hyperalgesia associated with surgical wounds. OPHTHALMIC FORMULATION: By July 1999, phase II clinical trials of ADL-2-1294 for the potential treatment of inflammatory corneal pain were underway. In June 1998, the FDA accepted an IND for ADL-2-1294 for the treatment of inflammatory pain associated with corneal abrasions, surgical and laser keratectomies and keratoconjunctivitis. By this time, a phase I study had been initiated to assess safety and efficacy parameters. By July 1997, an ophthalmic formulation was in preclinical development for the treatment of corneal hyperalgesia. In preclinical studies with the compound, efficacy was demonstrated in animal models of inflammatory pain. OTHER FORMULATIONS: By 1999, Adolor was also investigating mucosal, post-surgical and intra-articular indications for the compound. By 1996, Adolor had plans to carry out clinical development alone, up to and including phase II trials. Then, the company were to seek a corporate partner, probably from Japan, and hold on to US and European rights. Beyond phase III trials, Adolor had expected to sell the compound to a major US or European company. In 1997, Adolor licensed ADL-2-1294 to the South Korean OTC topically-administered epidermal analgesic. In July 1999, Adolor licensed worldwide (excluding Korea) prescription and OTC development and commercial rights to topical dermal ADL-2-1294, for use in the treatment of inflammatory pain, itching and other undisclosed indications, to SmithKline Beecham. The company was issued US-05849761 and US-05849762 in January 1999 covering the use of antidiarrheal opioid compounds for the treatment of inflammatory pain and the treatment of pruritus.

Journal Article↗
PubMed2005

Monitoring over-the-counter medication sales for early detection of disease outbreaks--New York City.

INTRODUCTION: Over-the-counter (OTC) medications are frequently used during the initial phase of illness, and increases in their sales might serve as an early indicator of communitywide disease outbreaks. Since August 2002, the New York City (NYC) Department of Health and Mental Hygiene (DOHMH) has tracked OTC medication sales to enhance detection of natural and intentional infectious disease outbreaks. OBJECTIVES: This report describes the surveillance system and presents results from retrospective analyses and a comparison between citywide trends in OTC medication sales and emergency department (ED) visits. METHODS: Sales data transmitted daily to DOHMH are categorized into two groups: influenza-like illness (ILI), which includes cough and influenza medications, and gastrointestinal illness (GI), which includes major brand and generic antidiarrheals. Cyclical, linear regression models were used to identify significant (p<0.05) increases in the daily ratio of ILI to analgesics sales (analgesics are used as a denominator in the absence of total sales). Daily and weekly average ratios of GI to analgesic sales were analyzed. Citywide trends in OTC ILI and GI medication sales were compared with ED visits for fever/influenza and diarrhea syndromes. RESULTS: Citywide ILI drug sales were highest during annual influenza epidemics and elevated during spring and fall allergy seasons, similar to trends in the ED fever/influenza syndrome. ILI sales did not consistently provide earlier warning than the ED system of communitywide influenza. GI drug sales increased during the fall and peaked during early winter and after the blackout of August 2003. Unlike ED diarrheal visits, GI medication sales did not substantially increase during late winter (February-March). CONCLUSION: Citywide OTC medication sales can provide indications of communitywide illness, including annual influenza epidemics. Antidiarrheal medication sales were more sensitive to increases in GI caused by norovirus and influenza than illness caused by rotavirus. OTC medication sales can be considered as an adjunct syndromic surveillance system but might not be as sensitive as ED systems.

Commerce↗
PubMedDate not supplied

Weekly administration of irinotecan (CPT-11) plus cisplatin for non-small cell lung cancer.

BACKGROUND: Weekly administration of irinotecan plus cisplatin was evaluated for untreated patients with non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Sixty mg/m(2) of irinotecan plus 30 mg/m(2) of cisplatin were administered on days 1, 8 and 15 every 4 weeks. Patients with no evidence of disease progression were treated with at least two cycles (8 weeks). Of the 39 patients, 29 were provided an antidiarrheal program consisting of sodium bicarbonate and magnesium oxide. RESULTS: There were 13 partial responses and an overall response rate of 33.3% [95% CI: 20%-50%]. The median time to progression and survival were 64 days and 12.8 months, respectively. Grade 4 neutropenia occurred in 15.4% of the patients, and Grade 3 and 4 diarrhea was observed in 12.8% and 2.6%, respectively. The incidence of leukopenia of grade 3-4 was significantly lower in patients provided with the antidiarrheal program due to lack of decrease in the lymphocyte count. CONCLUSION: This phase II study indicated that weekly irinotecan plus cisplatin administration was a promising treatment for untreated NSCLC.

Adult↗
PubMed1987

Ricinoleic acid and loperamide have opposite motor effects in the small and large intestine of the cat.

The actions of laxatives and antidiarrheal agents in the gut are incompletely understood. Therefore, the effects of Na ricinoleate 10(-4)-10(-2) g/kg b. w. and of loperamide 10(-4) g/kg b. w. on myoelectric activity and marker propulsion were studied in the small and large intestine of 7 unanesthetized cats. Intraduodenal application of ricinoleate briefly increased and then decreased spike activity in the small intestine; marker transit was delayed (92 +/- 18 min vs. 55 +/- 14 min in controls). Ricinoleate also initiated spike complexes of 10-215 sec duration. Transit from the right to the left colon was sometimes accelerated and sometimes delayed. The number of uncoupled slow waves was increased to 278% of control. Loperamide accelerated small intestinal transit to 17 +/- 6 min and markedly delayed it in the colon. At the same time it caused a strong and prolonged rise in colonic spike activity. When ricinoleate and loperamide were given together, their effects almost compensated for each other. The resulting net effect was similar to the data in the control experiments. It is concluded that laxatives and antidiarrheal agents alter not only transit, but also myoelectric activity in the small and large intestine. The effects are largely in opposite direction. Loperamide may, therefore, antagonize motor effects of ricinoleate in the gut.

Animals↗
PubMed1979

[Special consideration of clinical and travelling medical criteria (author's transl)].

The pharmacological properties of difenoxin hydrochloride, a meperidine derivative exerting antidiarrheal effect, are presented. The drug is compared with related substances such as diphenoxylate hydrochloride and loperamide. In an open multicentre study including 259 patients with acute or chronic diarrhea of various etiology, difenoxin hydrochloride removed the complaints in 63--75% of the cases and improved them in some further 20%. Mild side effects were seen in 4% of the cases. In view of the necessity to obtain immediate therapeutic results such an antidiarrheal may be prescribed in cases of traveler's diarrhea despite certain doubts. However, the patients should be warned to see a doctor if certain symptoms appeared.

Diarrhea↗