Trial reportClinical pharmacokinetics2007
Increased absorption of digoxin from the human jejunum due to inhibition of intestinal transporter-mediated efflux.
Trial report in Clinical pharmacokinetics, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 74 citations in OpenAlex.
- A phenotype-genotype approach to predicting CYP450 and P-glycoprotein drug interactions with the mixed inhibitor/inducer tipranavir/ritonavir.Clinical pharmacology and therapeutics · 2010Trial
- Estimating Human Jejunal Effective Permeability Using Numerical Deconvolution of Oral Solution Concentration Data.Pharmaceutical research · 2026Article
- Nanoparticle-Based Targeted Drug Delivery Methods for Heart-Specific Distribution in Cardiovascular Therapy.Pharmaceutics · 2025Review
- The Role of ABCB1, ABCG2, and SLC Transporters in Pharmacokinetic Parameters of Selected Drugs and Their Involvement in Drug-Drug Interactions.Membranes · 2024Review
- Evaluation of Drug-Drug Interactions of Rucaparib and CYP1A2, CYP2C9, CYP2C19, CYP3A, and P-gp Substrates in Patients With an Advanced Solid Tumor.Clinical and translational science · 2019Article
- Projecting ADME Behavior and Drug-Drug Interactions in Early Discovery and Development: Application of the Extended Clearance Classification System.Pharmaceutical research · 2016Article
- Intracellular accumulation of Praziquantel in T lymphoblastoid cell lines, CEM (parental) and CEMVBL(P-gp-overexpressing).BMC pharmacology & toxicology · 2016Article
- The Effects of Pregnenolone 16α-Carbonitrile Dosing on Digoxin Pharmacokinetics and Intestinal Absorption in the Rat.Pharmaceutics · 2010Article
- Tigecycline and cyclosporine interaction-an interesting case of biliary-excreted drug enhancing the oral bioavailability of cyclosporine.European journal of clinical pharmacology · 2009Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesThe contribution of transport in the small intestine by the apically located efflux pump P-glycoprotein to variable drug absorption in humans is still poorly understood. We therefore investigated whether inhibition of intestinal P-glycoprotein-mediated efflux by quinidine leads to increased absorption of the P-glycoprotein substrate digoxin.
methodsUsing a multilumen perfusion catheter, we investigated the impact of P-glycoprotein inhibition on absorption of two compounds: the P-glycoprotein substrate digoxin and the marker for passive transcellular absorption antipyrine. Two 20cm adjacent jejunal segments were isolated with the multilumen perfusion catheter in seven healthy subjects. Unlabelled and deuterated digoxin and antipyrine, respectively, were simultaneously infused into either of the intestinal segments. One of the segments was additionally perfused with the P-glycoprotein inhibitor quinidine. Intestinal perfusates were collected for 3 hours, and drug concentrations were determined in the intestinal perfusates, plasma and urine.
resultsQuinidine did not affect the disposition of antipyrine. In contrast, coadministration of quinidine into one jejunal segment caused a considerable increase in the amount of digoxin absorbed from this segment compared with the absorption from the other quinidine-free segment (22.3 +/- 8.9% vs 55.8 +/- 21.2% of the dose; p < 0.05). Accordingly, the area under the plasma concentration-time curve and the maximum plasma concentration of digoxin were considerably higher when luminal quinidine was coadministered (p < 0.05 and p < 0.001, respectively). Differences in digoxin absorption from the two intestinal segments were also reflected by pronounced differences in urinary digoxin elimination (5.5 +/- 3.3% vs 19.2 +/- 8.1% of the dose; p < 0.01).
conclusionsP-glycoprotein inhibition in enterocytes increases systemic exposure of orally administered drugs that are P-glycoprotein substrates. These data highlight the importance of the small intestine as an active barrier against xenobiotics.
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