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Updated: Jul 16, 2026
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Structural Biology and Analytical Chemistry Approaches for Characterizing C-Glycoside Metabolic Enzymes in Human Gut Microbiota
Published on: May 23, 2025
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.
Summary
P-glycoprotein (Pgp) activity, crucial for drug absorption, is boosted by rifampicin and linked to the MDR1 gene
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.
