P-glycoprotein efflux

D. J., Jeffrey, P. Improving the in vitro prediction of in vivo centtal nervous system penetration Integrating permeability, P-glycoprotein efflux, and free fractions in blood and brain. 

Smith, B. J., Doran, A. C., Mclean, S., Tingley III, F. D., O Neil, C. A., Kajiji, S. M., P-glycoprotein efflux at the blood-brain barrier mediates differences in brain disposition and pharmacodynamics between two structurally related neurokinin-1 receptor antagonists, J. Pharmacol. Exp. Ther. 2001, 298, 1252-1259. 

Johnson, B. M., Charman, W. N., Porter, C. J., The impact of P-glycoprotein efflux on enterocyte residence time and enterocyte-based metabolism of verapamil, J. Pharm. Pharmacol. 2001, 53, 1611-1619. 

S., Couet, W., In vitro and in vivo investigations on fluoroquinolones efFects of the P-glycoprotein efflux transporter on brain distribution of sparfloxadn, Eur. J. Pharm. Sci. 2000, 12, 85-93. 

Cabrera et al. [50] modeled a set of 163 drugs using TOPS-MODE descriptors with a linear discriminant model to predict p-glycoprotein efflux. Model accuracy was 81% for the training set and 77.5% for a validation set of 40 molecules. A "combinatorial QSAR" approach was used by de Lima et al. [51] to test multiple model types (kNN, decision tree, binary QSAR, SVM) with multiple descriptor sets from various software packages (MolconnZ, Atom Pair, VoSurf, MOE) for the prediction of p-glycoprotein substrates for a dataset of 192 molecules. Best overall performance on a test set of 51 molecules was achieved with an SVM and AP or VolSurf descriptors (81% accuracy each). 

Hamilton KO, Backstrom G, Yazdanian MA, Audus KL (2001) P-glycoprotein efflux pump expression and activity in Calu-3 cells. J Pharm Sci 90(5) 647-658. 

Batrakova, E., et al. 2001. Mechanism of pluronic effect on P-glycoprotein efflux system in blood-brain barrier Contributions of energy depletion and membrane fluidization. J Pharmacol Exp Ther 299 483. 

Sharom FJ. The P-glycoprotein efflux pump how does it transport drugs J Membr Biol 1997 160(3) 161 175. 

Plicamycin [plick a MYE sin] (mithramycin) also exerts its cytotoxicity through restriction of DNA-directed RNA synthesis. Resistance is due to P-glycoprotein efflux. Plicamycin has a relative toxic specificity for osteoclasts preventing their resorption, and lowers plasma calcium concentration in hypercalcemic patients—especially those with bone tumors. Toxicities include hemorrhage as well as effects on the bone marrow, liver, and kidneys. 

Kastin AJ, Fasold MB, Zadina JE (2002) Endomorphins, Met-enkephahn, Tyr-MlF-1 and the P-glycoprotein efflux system. Drug Metab Dispos 30 231-234. 

Chishty M, Reichel A, Siva J, Abbott NJ, Begley DJ. 2001. Affinity for the P-glycoprotein efflux pump at the blood-brain barrier may explain the lack of CNS side-effects of modern antihistamines. J. Drug Target 93 223-28... 

Sarkar, M.A. (1995) Quercetin not only inhibits P-glycoprotein efflux activity but also inhibits CYP3A isozymes. Cancer Chemother. Pharmacol. 36, 448-450. 

Kalvass JC, Maurer TS, Pollack GM (2007) Use of plasma and brain unbound fractions to assess the extent of brain distribution of 34 drugs comparison of unbound concentration ratios to in vivo p-glycoprotein efflux ratios. Drug Metab Dispos 35(4) 660-666... 

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