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At least 19 recordsLinked to original sources
PubMed1987

The evaluation and application of a radioimmunoassay for the measurement of diphenoxylic acid, the major metabolite of diphenoxylate hydrochloride (Lomotil), in human plasma.

Antibodies to diphenoxylic acid, the pharmacologically active metabolite of Lomotil, were successfully used to develop a precise and specific radioimmunoassay for the measurement of diphenoxylic acid in human plasma. The observed cross-reaction of the antiserum with Lomotil (23.5%) and p-hydroxy diphenoxylic acid (2.9%) was not considered to affect significantly the accuracy of the direct determination of diphenoxylic acid in plasma from human volunteers after ingestion of Lomotil tablets. Within-day and between-day coefficients of variation were better than 3 and 6%, respectively, over the concentration range of 3.4 to 255 ng ml-1. Comparable precision could be achieved at 2 ng ml-1 by doubling the volume of sample analyzed. The assay was used to measure plasma concentrations of diphenoxylic acid in 12 human volunteers for up to 24 hr after ingestion of Lomotil (10mg) tablets. Plasma diphenoxyllic acid levels rose to a mean (SE) maximum level of 87.8 (2.7) ng ml-1 3.3 (0.3) hr after dosing. By 24 hr after dosing plasma levls had decreased to 14.26 (1.67) ng ml-1. The appearance and elimination of plasma diphenoxylic acid could be described by a biexponential function. The appearance half-life was calculated to be 0.82 (0.09) hr, and the elimination half-life was 7.24 (0.73) hr.

Diphenoxylate↗
PubMed1980

Double-blind cross-over study comparing loperamide, codeine and diphenoxylate in the treatment of chronic diarrhea.

As no adequate comparison of these widely used drugs has been made, we have performed a double-blind cross-over trial in 30 individuals with chronic diarrhea. Each underwent three randomized treatment periods of 4 wk duration. Patients were instructed to increase the daily dose gradually until control was achieved or side effects became intolerable. Stool frequency, consistency, urgency, and incontinence were then compared when a stable dose was reached. Though 2.3 capsules (4.6 mg) of loperamide, 2.3 capsules (103.5 mg) of codeine and 2.5 capsulses (12.5 mg) of diphenoxylate all reduced stool frequency to the same extent, diphenoxylate was significantly less effective in producing a solid stool. Before treatment 95% of patients experienced urgency, sometimes associated with fecal incontinence, often as their major diability. Loperamide and codeine were more effective in relieving this than was diphenoxylate. Side effects, particularly central nervous effects, were greatest with diphenoxylate and least with loperamide. Approximately equal numbers discontinued each preparation; poor control and central-nervous-system side effects were the usual reasons for stopping diphenoxylate and codeine, and abdominal pain and constipation for stopping loperamide. We conclude that both loperamide and codeine phosphate are superior to diphenoxylate in the symptomatic treatment of chronic diarrhea.

Antidiarrheals↗
PubMed1975

Effects of E prostaglandins, diphenoxylate and morphine on intestinal motility in vivo.

The mechanism of the gastrointestinal motility effects of diphenoxylate and morphine in preventing E prostaglandin (PG) diarrhea was investigated. Duodenal motility studies were conducted in the anesthetized dog. Two contractile force transducers were oriented to record contractions from both the circular and longitudinal muscles. In some experiments the basic electrical rhythm (BER) was also recorded. Blood pressure was monitored from the femoral artery and drug injections were made in the femoral vein. Diphenoxylate shared with morphine the capacity to stimulate circular muscle contractions which correlated with the appearance of spike potentials on the BER. Prostaglandin E1 methyl ester (PGE1ME) showed marked relaxation of the circular muscle and abolishment of spike potentials. PGE1ME also blocked the stimulatory effects of diphenoxylate and morphine on the circular muscle. PGE1ME and PGE2 were found to be equally potent in producing diarrhea in mice. Diphenoxylate and morphine were found to be equally potent in inhibiting PG's diarrhea. These studies suggest that the constipating actions of diphenoxylate and morphine are a consequence of the increased circular muscle activity of the intestine.

Animals↗
PubMed1981

A comparative study of loperamide and diphenoxylate in the treatment of chronic diarrhoea caused by intestinal resection.

A double-blind cross-over study of the antidiarrhoeal effects of loperamide and diphenoxylate in 29 patients with chronic diarrhoea due to intestinal resection is presented. Most of these subjects had had surgery for Crohn's disease which was in a stable and nonactive phase during the study. Loperamide and diphenoxylate were presented as identical capsules. Each was administered for a minimum duration of 25 days. The number of capsules required to control diarrhoea was significantly smaller in the loperamide group than in the diphenoxylate group. Loperamide was also statistically superior to diphenoxylate at reducing the number of stools and improving the faecal consistency. Nineteen of the 29 patients considered loperamide to be the most effective antidiarrhoeal drug, five preferred diphenoxylate and five did not notice any difference.

Adult↗
PubMed1975

In vitro adsorption of diphenoxylate hydrochloride on activated charcoal and its relationship to pharmacological effects of drug in vivo. I.

The adsorption of diphenoxylate hydrochloride, a potent antidiarrheal agent, on activated charcoal powder was studied in vitro. Langmuir adsorption isotherms were established at pH 4 and 7, and the maximum adsorption capacity of charcoal for this drug was estimated using these values. Activated charcoal modified the bioavailability of diphenoxylate hydrochloride in vivo. The antipropulsive action of diphenoxylate in the mouse was strongly inhibited in the presence of activated charcoal. A comparative evaluation of charcoal and chromium oxide used as inert, nonabsorbable markers revealed that chromium oxide may be the marker of choic in GI transit studies in laboratory animals since it does not influence the bioavailability of diphenoxylate hydrochloride.

Adsorption↗
PubMed2003

Potential roles of P-gp and calcium channels in loperamide and diphenoxylate transport.

This study examined the accumulation and transport of two related systemic opioids used as antidiarrhoeal drugs and compared their rates of transport with known P-glycoprotein (P-gp) substrates used in our in vitro environment. Cellular uptake and efflux and transcellular transport were all determined using Caco-2 cells after exposure to loperamide or diphenoxylate, with or without a range of efflux inhibitors. Bidirectional transport studies of 5 microM loperamide showed efflux to be fivefold higher than influx (42 x 10(-6) compared to 8 x 10(-6) cm/s); however, this decreased to twofold at 10 microM and was abolished using 100 microM loperamide. An uptake pathway was also discovered when P-gp was inhibited which, in the presence of Ca(2+) channel blockers, was amplified, providing a potential mechanism for central nervous system effects to be increased upon blockage of L-type calcium channels, quite separate from any P-gp inhibition. Diphenoxylate transport, however, showed little sign of P-gp-mediated efflux. Diphenoxylate accumulated readily within cells, yet transport through cells was very low. Additionally, efflux inhibitors had little impact on transport or accumulation, suggesting that diphenoxylate was not a substrate for an efflux mechanism.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1976

Unfavorable effect of atropine-diphenoxylate (Lomotil) therapy in lincomycin-caused diarrhea.

In this double-blind, randomized study, 200 normal subjects received a three-day course of one of five treatment regimens: lincomycin hydrochloride monohydrate injection (sterile solution, 300 mg/ml) with two tablets of either placebo, a mixture of atropine sulfate and diphenoxylate hydrochloride (Lomotil), an aspirin-phenacetin-caffeine (APC) combination or the latter with codeine, or an injection of saline with two placebo tablets. Gastrointestinal irritation was most prominent in subjects receiving lincomycin with atropine-diphenoxylate and lincomycin with APC plus codeine (P less than .05). Decreased intestinal motility from atropine-diphenoxylate or codeine may increase the contact time between the lincomycin (or its metabolites) or some developing toxic substances and the mucosal epithelium. The use of atropine-diphenoxylate or codeine in treating lincomycin-induced diarrhea may be questionable.

Administration, Oral↗
PubMed1975

An X-ray study on the acute action of diphenoxylate on the intestinal motility in volunteers.

The intestinal inhibitory activity of 1-(3-cyano-3,3-diphenylpropyl)-4-phenyl-4-piperidine-carboxylic acid ethyl ester (diphenoxylate) after a single oral dose of 5 mg was studied in 10 volunteers with X-ray diagnostic methods. The diphenoxylate treatment lengthened the transit time of the barium sulphate to caecum from 3.2 to 4.3 h. The X-ray cinematography showed the slower duodenal emptying in 5/10 of the subjects, but only in 1 of these the velocity of the peristaltic wave was clearly decreased. The results demonstrate directly the acute inhibitory action of diphenoxylate on intestinal motility with the dose used generally 3--4 times daily for the symptomatic treatment of diarrhoea.

Adult↗
PubMed1975

The constipating effect of diphenoxylate (Retardinr) in ulcerative colitis. A double-blind controlled trial.

A double-blind study of 20 patients with ulcerative colitis during treatment with diphenoxylate 5 mg three times daily and placebo is reported. There were two treatment periods of 14 days each, with cross-over technique and randomized sequence. Test variable for constipating effect was the mean number of defaecations per day. The criterion for inclusion of patients was the presence of 4 or more daily bowel movements; 2 patients did not complete the investigation. Significant difference (p less than 0.01) in constipating effect between diphenoxylase and placebo was demonstrated both during a period of 12 days and a period of 6 days (Tables II and III). The average number of bowel movements were reduced by 0.7 and 1.3 per day respectively. Side-effects during treatment with diphenoxylate were seen in 53% (Table III) with significant difference against placebo (p less than 0.05). On the basis of the small absolute reduction of defaecation frequency side-effects, it is concluded that diphenoxylate has no place in the routine treatment of ulcerative colitis.

Adolescent↗
PubMed1991

Diphenoxylate-atropine (Lomotil) overdose in children: an update (report of eight cases and review of the literature)

Eight pediatric accidental overdoses of diphenoxylate-atropine (Lomotil) are reported, and 28 literature cases are reviewed. This overdose is primarily an opioid intoxication, occasionally associated with atropine toxicity. Only 6 of 36 children showed signs of atropine overdose (central nervous system excitement, hypertension, fever, flushed dry skin). Contrary to popular belief, atropine effects occur before, during, or after opioid effects. Opioid overdose (central nervous system and respiratory depression with miosis) predominated or occurred without any signs of atropine toxicity in 33 cases (92%). Diphenoxylate-induced hypoxia was the major problem and was associated with slow or fast respirations, hypotonia or rigidity, cardiac arrest, and in 3 cases cerebral edema and death. Respiratory depression recurred 13 to 24 hours after the ingestion in 7 cases and was probably due to accumulation of difenoxine, an active metabolite of diphenoxylate. Recommended treatment is intravenous naloxone for depressed or inadequate respirations, followed by continuous intravenous naloxone infusion, prompt gastric lavage, repeated administration of activated charcoal, and close monitoring for 24 hours.

Atropine↗
PubMedDate not supplied

[Intoxication by diphenoxylate (author's transl)].

Two cases of intoxication by diphenoxylate, inespecific antidiarrheal, depressor of the intestinal motility, are presented. Diphenoxylate is chemically related with meperidine. One case was caused by hipersensitivity and the other one by overdose. Both had a favourable outcome. Existent bibliography was reviewed and clinical signs of this intoxication pointed-out. It is suggested that diphenoxylate should not be prescribed to children under thirty months.

Child, Preschool↗
PubMed1977

Determination of diphenoxylate hydrochloride and atropine sulfate in solutions and tablets.

Methods for the determination of diphenoxylate hydrochloride and atropine sulfate combinations in solutions and powdered tablet composites are presented. A semiautomated assay for diphenoxylate hydrochloride in individual tablets (content uniformity) also is presented. The USP XIX assays for these products are cumbersome and, in the case of solutions, inaccurate due to spectral interferences; the proposed methods offer substantial improvements in sensitivity, specificity, and speed. Results obtained by the USP and proposed methods are compared for several lots of commercial products. The accuracy and precision of the proposed methods are shown by standard recovery studies.

Atropine↗
PubMed1987

Effect of liquid diphenoxylate hydrochloride and atropine sulfate (Lomotil) instillations on dynamics and function of continent cecal urinary reservoirs.

We assessed the impact of twice daily instillations of 10 ml. liquid diphenoxylate hydrochloride and atropine sulfate (Lomotil) on the dynamics and function of continent urinary reservoirs constructed from intact cecum and ascending colon. Six patients were treated for 1 to 3 weeks at 3 to 8 months postoperatively. The treatments reduced the frequency of spontaneous reservoir contractions, as well as the basal and contraction pressures of the reservoirs. The reservoir capacities were increased modestly. These alterations in reservoir dynamics were accompanied by a decrease in the cramping characteristically associated with reservoir distension and increased intervals between reservoir catheterization. Two patients who had incontinence after initially successful operations regained continence during treatment. No systemic side effects were observed, although dilution of the drug may be required to prevent reservoir irritability. Diphenoxylate hydrochloride and atropine sulfate instillations may prevent acute and possibly long-term pressure-related complications of continent urinary reservoirs constructed from intact cecum and ascending colon.

Atropine↗
PubMed1977

Prostaglandin-induced diarrhoea treated with loperamide or diphenoxylate. A double-blind study.

Loperamide was compared double-blind with diphenoxylate and a placebo in 59 women with diarrhoea due to prostaglandin administration for mid-trimester abortion. Treatment was started with the intake of two capsules two hours before the first intramuscular injection of 15(S-)15 methyl prostaglandin F2alpha and was then adapted individually, i.e. one capsule after each unformed stool, with a maximum of ten per 24 hours. Both antidiarrhoeals were significantly more effective than the placebo in preventing diarrhoea, and loperamide was found to be more active than diphenoxylate. The course of abortion, BP and vital signs, or prostaglandin side-effects other than diarrhoea were not affected by either antidiarrhoeal, nor could any adverse experience be specifically attributed to them.

Abortion, Induced↗