Drug Information

Drug (ID: DG00158) and It's Reported Resistant Information

• Name: Loperamide
• Synonyms: Ioperamide; Loperacap; Loperamida; Loperamidum; Kaopectate II; Loperamide Monohydrochloride; Pepto Diarrhea Control; Apo-Loperamide; Diamide (TN); Diarr-Eze; Dimor (TN); Imodium (TN); Imodium A-D Caplets; Loperamida [INN-Spanish]; Loperamide (INN); Loperamide [INN:BAN]; Loperamidum [INN-Latin]; Lopex (TN); Maalox Anti-Diarrheal; Nu-Loperamide; PMS-Loperamide; Pepto (TN); R-18553; Rho-Loperamide
• Indication:
  In total 1 Indication(s)
  Bowel habit change [ICD-11: ME05]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Diarrhea [ICD-11: DA90]; [2]
• Target: Opioid receptor delta (OPRD1); OPRD_HUMAN; [1]
• Formula: C29H33ClN2O2
• IsoSMILES: CN(C)C(=O)C(CCN1CCC(CC1)(C2=CC=C(C=C2)Cl)O)(C3=CC=CC=C3)C4=CC=CC=C4
• InChI: 1S/C29H33ClN2O2/c1-31(2)27(33)29(24-9-5-3-6-10-24,25-11-7-4-8-12-25)19-22-32-20-17-28(34,18-21-32)23-13-15-26(30)16-14-23/h3-16,34H,17-22H2,1-2H3
• InChIKey: RDOIQAHITMMDAJ-UHFFFAOYSA-N
• PubChem CID: 3955
• ChEBI ID: CHEBI:6532
• TTD Drug ID: D0CS2F
• VARIDT ID: DR00171
• DrugBank ID: DB00836

Type(s) of Resistant Mechanism of This Drug

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-13: Digestive system diseases

Diarrhea [ICD-11: DA90]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [2]

• Molecule Alteration: Activity; Up-regulation
• Resistant Disease: Diarrhea [ICD-11: DA90.0]
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: CaCo2 cells; Colon; Homo sapiens (Human); CVCL_0025
• Experiment for Molecule Alteration: In vitro Caco-2 cell permeability experiments assay
• Experiment for Drug Resistance: Respiration assessments assay
• Mechanism Description: P-glycoprotein is an ATP-dependent efflux pump that transports a wide variety of agents out of cells at the blood-brain barrier, thereby restricting CNS penetration of many drugs, including LOP. TPV is a substrate for and an inducer of P-gp activity.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [3]

• Molecule Alteration: Missense mutation; Haplotype G2677/T3435
• Sensitive Disease: Diarrhea [ICD-11: DA90.0]
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Genotyping assay
• Experiment for Drug Resistance: Assessment of central opioid effects assay
• Mechanism Description: The results support a functional importance of the ABCB1 genetic variants for the pharmacokinetics of loperamide. Highest loperamide plasma concentrations were seen in carriers of haplotype G2677.

ICD-21: Symptoms/clinical signs/unclassified clinical findings

Pain [ICD-11: MG30]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [1]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Pain [ICD-11: MG30.0]
• Experimental Note: Revealed Based on the Cell Line Data
• Experiment for Molecule Alteration: ATPase activity assay
• Mechanism Description: P-glycoprotein (Pgp) is a multidrug resistance transporter that limits the penetration of a wide range of neurotherapeutics into the brain including opioids. Pgp-knockout mice had more than a 10-fold higher level of loperamide in their brains than wild-type. Both rats and humans have shown elevated levels of loperamide in the presence of the Pgp-specific inhibitor cyclosporine A.

References

• Ref 1: A Conformationally Gated Model of Methadone and Loperamide Transport by P-Glycoprotein. J Pharm Sci. 2018 Jul;107(7):1937-1947. doi: 10.1016/j.xphs.2018.02.019. Epub 2018 Feb 28.
• Ref 2: Interaction of ritonavir-boosted tipranavir with loperamide does not result in loperamide-associated neurologic side effects in healthy volunteers. Antimicrob Agents Chemother. 2005 Dec;49(12):4903-10. doi: 10.1128/AAC.49.12.4903-4910.2005.
• Ref 3: Effects of ABCB1 (multidrug resistance transporter) gene mutations on disposition and central nervous effects of loperamide in healthy volunteers. Pharmacogenetics. 2003 Nov;13(11):651-60. doi: 10.1097/00008571-200311000-00001.