Membrane transporters in drug development
Overall, it is advised that the timing of transporter investigations should be driven by efficacy, safety and clinical trial enrolment questions, as well as a need for further understanding of the absorption, distribution, metabolism and excretion properties of the drug molecule, and information required for drug labelling.
The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors.
It is demonstrated that P-glycoprotein limits the oral bioavailability and penetration of these agents into the brain and raises the possibility that higher HIV-1 protease inhibitor concentrations may be obtained by targeted pharmacologic inhibition of P- glycoprotein transport activity.
OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine.
- M. Cvetković, B. Leake, M. Fromm, G. Wilkinson, R. Kim
- BiologyDrug Metabolism And Disposition
- 1 August 1999
OATP transporters and P-gp colocalize in organs of importance to drug disposition such as the liver, their activity provides an explanation for the heretofore unknown mechanism(s) responsible for fexofenadine's disposition and suggests potentially similar roles in the disposition of other xenobiotics.
Identification of functionally variant MDR1 alleles among European Americans and African Americans
Allelic variation in MDR1 is more common than previously recognized and involves multiple SNPs whose allelic frequencies vary between populations, and some of these SNPs are associated with altered P‐glycoprotein function.
Polymorphisms in Human MDR1 (P‐glycoprotein): Recent Advances and Clinical Relevance
Drug and bile acid transporters in rosuvastatin hepatic uptake: function, expression, and pharmacogenetics.
Multiple transporters mediate the overall hepatic uptake of rosuvastatin, and NTCP may be a heretofore unrecognized transporter important to the disposition of roviastatin and possibly other drugs/statins in clinical use.
The orphan nuclear receptor HNF4α determines PXR- and CAR-mediated xenobiotic induction of CYP3A4
It is shown that the orphan nuclear receptor hepatocyte nuclear factor-4α (HNF4α; HNF4A) is critically involved in the PXR- and CAR-mediated transcriptional activation of CYP3A4, an important regulator of coordinate nuclear-receptor–mediated response to xenobiotics.
Fruit juices inhibit organic anion transporting polypeptide–mediated drug uptake to decrease the oral availability of fexofenadine
Our objective was to examine the effect of different fruits and their constituents on P‐glycoprotein and organic anion transporting polypeptide (OATP) activities in vitro and on drug disposition in…
Polymorphisms in OATP-C
The presence of multiple functionally relevant single-nucleotide polymorphisms (SNPs) in OATP-C in a population of African- and European-Americans is demonstrated and may represent a heretofore unrecognized factor influencing drug disposition.
Polymorphisms in Human Organic Anion-transporting Polypeptide 1A2 (OATP1A2)
In vitro functional assessment revealed that the A516C and A404T variants had markedly reduced capacity for mediating the cellular uptake of OATP1A2 substrates and two δ-opioid receptor agonists, deltorphin II, and [d-penicillamine2,5]-enkephalin, while the G559A and C2003G variants appeared to have substrate-dependent changes in transport activity.