Drug/Small Molecule:
diphenoxylate

PharmGKB contains no dosing guidelines for this drug/small molecule. To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.

PharmGKB has no annotated drug labels with pharmacogenomic information for this drug/small molecule. If you know of a drug label with PGx, send us a message.

PharmGKB contains no Clinical Variants that meet the highest level of criteria.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

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This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Gene?
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • Dea No. 9170
  • Difenossilato [Dcit]
  • Difenoxilato [INN-Spanish]
  • Diphenoxalate
  • Diphenoxylate Hydrochloride
  • Diphenoxylatum [INN-Latin]
Trade Names
  • Lomotil
Brand Mixture Names
  • Lomotil (Atropine Sulfate + Diphenoxylate Hcl)

PharmGKB Accession Id:
PA164746539

Description

A meperidine congener used as an antidiarrheal, usually in combination with atropine. At high doses, it acts like morphine. Its unesterified metabolite difenoxin has similar properties and is used similarly. It has little or no analgesic activity. This medication is classified as a Schedule V under the Controlled Substances Act by the Food and Drug Administration (FDA) and the DEA in the United States when used in preparations. When diphenoxylate is used alone, it is classified as a Schedule II.

Source: Drug Bank

Indication

For as adjunctive therapy in the management of diarrhea

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Diphenoxylate is an opiate receptor agonists that stimulate mu receptors in GI to decrease the peristalsis and constrict the sphincters. Diphenoxylate has a direct effect on circular smooth muscle of the bowel, that conceivably results in segmentation and prolongation of gastrointestinal transit time. The clinical antidiarrheal action of diphenoxylate may thus be a consequence of enhanced segmentation that allows increased contact of the intraluminal contents with the intestinal mucosa.

Source: Drug Bank

Pharmacology

Diphenoxylate, an antidiarrheal, is effective as adjunctive therapy in the management of diarrhea. Diphenoxylate is rapidly and extensively metabolized in man by ester hydrolysis to diphenoxylic acid (difenoxine), which is biologically active and the major metabolite in the blood.

Source: Drug Bank

Food Interaction

Avoid alcohol.|Take with food.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic

Source: Drug Bank

Protein Binding

74-95%

Source: Drug Bank

Absorption

90%

Source: Drug Bank

Half-Life

12-14 hours

Source: Drug Bank

Toxicity

Coma, dry skin and mucous membranes, enlarged pupils of the eyes, extremely high body temperature, flushing, involuntary eyeball movement, lower than normal muscle tone, pinpoint pupils, rapid heartbeat, restlessness, sluggishness, suppressed breathing

Source: Drug Bank

Chemical Properties

Chemical Formula

C30H32N2O2

Source: Drug Bank

Isomeric SMILES

CCOC(=O)C1(CCN(CC1)CCC(C#N)(c2ccccc2)c3ccccc3)c4ccccc4

Source: OpenEye

Canonical SMILES

CCOC(=O)C1(CCN(CCC(C#N)(C2=CC=CC=C2)C2=CC=CC=C2)CC1)C1=CC=CC=C1

Source: Drug Bank

Average Molecular Weight

452.5873

Source: Drug Bank

Monoisotopic Molecular Weight

452.246378278

Source: Drug Bank

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Drug Targets

Gene Description
OPRD1 (source: Drug Bank)
OPRM1 (source: Drug Bank)

Drug Interactions

Drug Description
diphenoxylate Possible antagonism of action (source: Drug Bank)
diphenoxylate Possible antagonism of action (source: Drug Bank)

Relationships from National Drug File - Reference Terminology (NDF-RT)

May Treat
Contraindicated With

Publications related to diphenoxylate: 1

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Uniform assessment and ranking of opioid μ receptor binding constants for selected opioid drugs. Regulatory toxicology and pharmacology : RTP. 2011. Volpe Donna A, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
54868-0427-5
DrugBank:
DB01081
KEGG Drug:
D00301
PubChem Compound:
13505
PubChem Substance:
10074
46507130
ChemSpider:
12919
Therapeutic Targets Database:
DAP001136
FDA Drug Label at DailyMed:
d2b171be-ac59-48ec-84da-03d3f2d34ca6

Clinical Trials

These are trials that mention diphenoxylate and are related to either pharmacogenetics or pharmacogenomics.

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Sources for PharmGKB drug information: DrugBank, Open Eye Scientific Software.