Impact of Genetic Polymorphisms of ABCB1 (MDR1, P-Glycoprotein) on Drug Disposition and Potential Clinical Implications: Update of the Literature

@article{Wolking2015ImpactOG,
  title={Impact of Genetic Polymorphisms of ABCB1 (MDR1, P-Glycoprotein) on Drug Disposition and Potential Clinical Implications: Update of the Literature},
  author={Stefan Wolking and Elke Schaeffeler and Holger Lerche and Matthias Schwab and Anne T. Nies},
  journal={Clinical Pharmacokinetics},
  year={2015},
  volume={54},
  pages={709-735}
}
ATP-binding cassette transporter B1 (ABCB1; P-glycoprotein; multidrug resistance protein 1) is an adenosine triphosphate (ATP)-dependent efflux transporter located in the plasma membrane of many different cell types. Numerous structurally unrelated compounds, including drugs and environmental toxins, have been identified as substrates. ABCB1 limits the absorption of xenobiotics from the gut lumen, protects sensitive tissues (e.g. the brain, fetus and testes) from xenobiotics and is involved in… 

Effect of ABCB1 genetic polymorphisms on the transport of rivaroxaban in HEK293 recombinant cell lines

TLDR
It is suggested that the ABCB1 coding SNPs investigated in the present study are unlikely to contribute to the inter-individual variability in rivaroxaban plasma concentrations.

Combinations of common SNPs of the transporter gene ABCB1 influence apparent bioavailability, but not renal elimination of oral digoxin

TLDR
The population pharmacokinetic model supports the use of oral digoxin as a phenotyping substrate of intestinal P-gp, but not to assess renal P- gp activity, and the relationship between SNP combinations and digoxin pharmacokinetics was explored.

Effect of four ABCB1 genetic polymorphisms on the accumulation of darunavir in HEK293 recombinant cell lines

TLDR
It is demonstrated that while ABCB 1 expression limits intracellular accumulation of darunavir, there is no significant difference in efflux activity between cells expressing wild-type ABCB1 and those that express any of the studied variants.

Polymorphisms of ABCB1, CYP3A4 and CYP3A5 Genes in Ovarian Cancer and Treatment Response in Poles.

TLDR
Findings from this study may contribute to a better prediction of therapy outcome in Polish women and their response to treatment.

Relevance of Transporters in Clinical Studies

  • B. Hagenbuch
  • Biology, Medicine
    Drug Discovery and Evaluation: Methods in Clinical Pharmacology
  • 2020
TLDR
The Food and Drug Administration, the European Medicines Agency, and the Japanese Pharmaceuticals and Medical Devices Agency have identified seven transporters which need to be tested for investigational drug disposition, including two multidrug resistance protein 1 (MDR1) and the breast cancer resistance protein (BCRP).

Influence of Single Nucleotide Polymorphisms on Rifampin Pharmacokinetics in Tuberculosis Patients

TLDR
This narrative review aims to identify literature that has explored the influence of single nucleotide polymorphisms of genes encoding drug transporters and their transcriptional regulators, metabolizing enzymes, and VDR and its pathway regulators on plasma RF concentrations in TB patients on antitubercular therapy.

ABCB1, ABCG2 and CYP2D6 polymorphism effects on disposition and response to long-acting risperidone

...

References

SHOWING 1-10 OF 313 REFERENCES

Functional significance of genetic polymorphisms in P-glycoprotein (MDR1, ABCB1) and breast cancer resistance protein (BCRP, ABCG2).

  • I. Ieiri
  • Biology, Medicine
    Drug metabolism and pharmacokinetics
  • 2012
TLDR
The impact of PGx in ABC transporters in terms of PK/PD is explained, focusing on P-glycoprotein and breast cancer resistance protein (BCRP).

P-glycoprotein: tissue distribution, substrates, and functional consequences of genetic variations.

  • I. Cascorbi
  • Biology
    Handbook of experimental pharmacology
  • 2011
TLDR
Current knowledge of the functional significance genetic variants of ABC membrane transporters does not allow selection of a particular SNP to predict an individual's pharmacokinetics.

Clinical aspects of the MDR1 (ABCB1) gene polymorphism.

TLDR
The impact of MDR1 polymorphisms on pharmacokinetics and pharmacodynamics of Pgp substrates is moderate, and clinical studies on the effects of the C3435T polymorphism and drug treatment with cardiac glycosides, the immunosuppressants cyclosporine and tacrolimus, HIV protease inhibitors, and tricyclic antidepressants are discussed.

Modulation of multidrug resistance P-glycoprotein 1 (ABCB1) expression in human heart by hereditary polymorphisms.

TLDR
The present study based on auricular samples suggests that genetic factors play a rather limited role in modulating P- gp expression in human heart, and the substantial interindividual variability in cardiac P-gp expression is likely related to environmental or disease related factors.

Substrate-Dependent Effects of Human ABCB1 Coding Polymorphisms

TLDR
Functional data demonstrate that nonsynonymous polymorphisms in ABCB1 may selectively alter P-gp transport and drug-drug interactions in a substrate- and inhibitor-dependent manner.

Role of pharmacogenetics of ATP-binding cassette transporters in the pharmacokinetics of drugs.

MDR1 pharmacogenetics: frequency of the C3435T mutation in exon 26 is significantly influenced by ethnicity.

TLDR
The high frequency of the C allele in the African group implies overexpression of PGP and may have important therapeutic and prognostic implications for use of P GP dependent drugs in individuals of African origin.

MDR1 genotype-related pharmacokinetics: fact or fiction?

  • T. Sakaeda
  • Biology, Medicine
    Drug metabolism and pharmacokinetics
  • 2005
TLDR
This review summarizes the latest reports for the future individualization of pharmacotherapy based on MDR1 genotyping, and attempts to explain discrepancies in the results on C3435T.

Function-Altering SNPs in the Human Multidrug Transporter Gene ABCB1 Identified Using a Saccharomyces-Based Assay

TLDR
A robust new methodology for identification of function-altering polymorphisms in human multidrug transporter genes is established, identified polymorphisms affecting P-gp function are identified, and a step toward genotype-determined dosing of chemotherapeutics is provided.

The MDR1 (ABCB1) Gene Polymorphism and its Clinical Implications

TLDR
It is believed that further understanding the physiology and biochemistry of P-glycoprotein with respect to its genetic variations will be important to establish individualised pharmacotherapy with various clinically used drugs.
...