P-glycoprotein activity and biological response
| Autor: | Philippus Elsinga, W Vaalburg, van Aren Waarde, NH Hendrikse, Joost Bart |
|---|---|
| Přispěvatelé: | Guided Treatment in Optimal Selected Cancer Patients (GUTS), Targeted Gynaecologic Oncology (TARGON), Clinical pharmacology and pharmacy |
| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
Drug
media_common.quotation_subject Drug Resistance ATP-binding cassette transporter Pharmacology Toxicology Radioligand Assay Pharmacokinetics Genetic In vivo Cyclosporin a Animals Humans ATP Binding Cassette Transporter Subfamily B Member 1 Polymorphism P-glycoprotein media_common Polymorphism Genetic biology P-Glycoprotein Drug Resistance Multiple Multiple drug resistance Drug Resistance Neoplasm Positron-Emission Tomography biology.protein Neoplasm Efflux Multiple |
| Zdroj: | Vaalburg, W, Hendrikse, N H, Elsinga, P H, Bart, J & Van Waarde, A 2005, ' P-glycoprotein activity and biological response ', Toxicology and Applied Pharmacology, vol. 207, no. 2 SUPPL. https://doi.org/10.1016/j.taap.2005.03.027 Toxicology and Applied Pharmacology, 207(2 Suppl), 257-60. ACADEMIC PRESS INC ELSEVIER SCIENCE Toxicology and Applied Pharmacology, 207(2 SUPPL.). Academic Press Inc. |
| ISSN: | 0041-008X |
| DOI: | 10.1016/j.taap.2005.03.027 |
| Popis: | P-glycoprotein (P-gp) is a transmembrane drug efflux pump encoded by the MDR-1 gene in humans. Most likely P-gp protects organs against endogenous and exogenous toxins by extruding toxic compounds such as chemotherapeutics and other drugs. Many drugs are substrates for P-gp. Since P-gp is also expressed in the blood-brain barrier, P-gp substrates reach lower concentrations in the brain than in P-gp-negative tissues. Failure of response to chemotherapy of malignancies can be due to intrinsic or acquired drug resistance. Many tumors are multidrug resistant (MDR); resistant to several structurally unrelated chemotherapeutic agents. Several mechanisms are involved in MDR of which P-gp is studied most extensively. P-gp extrudes drugs out of tumor cells resulting in decreased intracellular drug concentrations, leading to the MDR phenotype. Furthermore, the MDR-1 gene exhibits several single nucleotide polymorphisms, some of which result in different transport capabilities. P-gp functionality and the effect of P-gp modulation on the pharmacokinetics of novel and established drugs can be studied in vivo by positron emission tomography (PET) using carbon-11 and fluorine-18-labeled P-gp substrates and modulators. PET may demonstrate the consequences of genetic differences on tissue pharmacokinetics. Inhibitors such as calcium-channel blockers (verapamil), cyclosporin A, ONT-093, and XR9576 can modulate the P-gp functionality. With PET the effect of P-gp modulation on the bioavailability of drugs can be investigated in humans in vivo. PET also allows the measurement of the efficacy of newly developed P-gp modulators. |
| Databáze: | OpenAIRE |
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