Drug Efflux Transporters

Another limitation is that there is no quantitative relationship between active drug transport in the cell culture models and in vivo e.g. [92, 93]. The reason may be that the expression level of the transporter in Caco-2 cells is not comparable to that in vivo or that there is a difference in effective surface area (see Section 4.3.2.2 below). One solution to this problem is to determine the apparent transport constants, Km and Vmax, for each transporter and subsequently, to determine a scaling factor. However, this is not readily done. In addition these studies are further complicated by the lack of specific substrates. For example, there are almost no specific substrates for the drug efflux transporters [18]. Therefore, other epithelial... 

Tab. 9.3 Summary of genetic poly morphisms in drug efflux transporters ...

Schinkel, A.H. and Jonker, J.W. (2003) Mammalian drug efflux transporters of the ATP binding cassette (ABC) family an overview. Advanced Drug Delivery Reviews, 55, 3-29. 

Zhang, Y., Bachmeier, C. and Miller, D.W. (2003) In vitro and in vivo models for assessing drug efflux transporter activity. Advanced Drug Delivery Reviews, 55, 31-51. 

C.J. Bachmeier, T.J. Spitzenberger, W.F. Elmquist, and D.W. Miller. Quantitative assessment of HIV-1 protease inhibitor interactions with drug efflux transporters in the blood-brain barrier. Pharm Res. 22 1259-1268 (2005). 

Role of Drug Efflux Transport Systems in the Blood-Brain Barrier..604... 

Batrakova, E., et al. 2003. Optimal structure requirements for pluronic block copolymers in modifying P-glycoprotein drug efflux transporter activity in bovine brain microvessel endothelial cells. J Pharmacol Exp Ther 304 845. 

Batrakova, E.V., et al. 2004. Effect of Pluronic P85 on ATPase activity of drug efflux transporters. Pharm Res 21 2226. 

Kabanov, A. Y., E.V. Batrakova, and D.W. Miller. 2003. Pluronic block copolymers as modulators of drug efflux transporter activity in the blood-brain barrier. Adv Drug Deliv Rev 55 151. 

Dhar S, Nygren P, Liminga G, et al. Relationship between cytotoxic drug response patterns and activity of drug efflux transporters mediating multidrug resistance. Eur J Pharmacol 1998 346(2-3) 315-322. 

Describe three generations of inlubitors of drug efflux transporters in the BBB. 

Loscher W, Potschka H (2005b) Role of drug efflux transporters in tire brain for dr ug disposition and treatment of brain diseases. Prog Neurobiol 76 22—76. 

Explain how the drug efflux transporters affect drug transport to the brain List examples of drug efflux transporters expressed in the BBB. 

---