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Related Experiment Video

Updated: Jul 16, 2026

Structural Biology and Analytical Chemistry Approaches for Characterizing C-Glycoside Metabolic Enzymes in Human Gut Microbiota
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Human intestinal P-glycoprotein activity estimated by the model substrate digoxin.

U L Larsen1, L Hyldahl Olesen, C Guldborg Nyvold

  • 1Department of Internal Medicine, Viborg County Hospital, Viborg, Denmark.

Scandinavian Journal of Clinical and Laboratory Investigation
|March 17, 2007
PubMed
Summary

P-glycoprotein (Pgp) activity, crucial for drug absorption, is boosted by rifampicin and linked to the MDR1 gene

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Area of Science:

  • Pharmacology
  • Genetics
  • Gastroenterology

Background:

  • P-glycoprotein (Pgp) influences intestinal xenobiotic uptake and is implicated in ulcerative colitis susceptibility.
  • Understanding Pgp activity is vital for predicting drug response and disease risk.

Purpose of the Study:

  • To investigate Pgp activity in relation to age, gender, drug treatment (rifampicin, ketoconazole), and MDR1 gene polymorphisms (G2677T, C3435T).
  • To assess the impact of these factors on Pgp function using digoxin as a model drug.

Main Methods:

  • Pgp activity assessed via digoxin pharmacokinetics in 32 healthy subjects.
  • MDR1 gene expression analyzed in duodenal biopsies using RQ-PCR and Western blot.
  • MDR1 single nucleotide polymorphisms (SNPs) identified by PCR-RFLP.
  • Drug treatment effects evaluated in a randomized, cross-over design.

Main Results:

  • Rifampicin significantly increased Pgp activity, MDR1 mRNA, and Pgp levels (p<0.05).
  • Higher Pgp activity observed in individuals with the MDR1 3435 wild-type (CC) genotype (p<0.05).
  • No significant association found between Pgp activity and age, gender, or the MDR1 G2677T SNP.

Conclusions:

  • Rifampicin enhances Pgp activity by upregulating MDR1 mRNA and Pgp expression.
  • The MDR1 3435 wild-type allele is associated with increased Pgp activity.
  • These findings reinforce the role of Pgp in treatment response and disease susceptibility.