Drug disposition transporters

Importantly, the currently available transporter models only cover a small fraction of all transporters involved in drug disposition. Other than incorporating current stand-alone transporter models into systemic models to directly predict drug pharmacokinetic properties, continued efforts are still needed to investigate other transporters such as MRP, BCRP, NTCP, and OAT, to get a more complete understanding of the drug pharmacokinetic profile. 

Schuetz EG, Schinkel AH. Drug disposition as determined by the interplay between drug-transporting and drug-metabolizing systems. J Biochem Mol Toxicol 1999 13[3—4] 219—222. 

The role of other ABC-efHux transporters (ATP-binding cassette transporters) such as MRPs and BCRP was also intensively investigated over the past decade. However, most studies investigating the importance of ABC transporters for drug disposition were performed with different cell lines and animal models. In comparison to P-glycoprotein, only limited human data are available about the role of ABC transporters on drug disposition. In this chapter mainly human data will be discussed. For more detailed description and in vitro data about MRPs see Section 15.3. 

Polarized tissues directly involved in drug absorption (intestine) or excretion (liver and kidney) and restricted drug disposition (blood-tissue barriers) asymmetrically express a variety of different drug transporters in the apical or basolateral membrane resulting in vectorial dmg transport. This vectorial dmg transport is characterized by two transport processes the uptake into the cell and subsequently the directed elimination out of the cell (Figure 15.3). Because the uptake of substances... 

Multidrug Resistance Proteins and Drug Transport 346 Role of P-Glycoprotein for Drug Disposition 349 Vectorial Drug Transport 352 References 355... 

Goh LB, Spears KJ, Yao DG, Ayrton A, Morgan P, Wolf CR and Friedberg T (2002) Endogenous Drug Transporters in In Vitro and In Vivo Models for the Prediction of Drug Disposition in Man. Biochem Pharmacol 64 pp 1569-1578. 

The following sections provide an overview of the application of the IPL for the study of drug absorption. Examples are provided to illustrate the use of the IPL to study drug permeability, absorption profiles, transport mechanisms and the effects of inhaled dose formulation on drug disposition. 

Wu C-Y, Benet LZ (2005) Predicting Drug Disposition via Application of BCS Transport/Absorption/Elimination Interplay and Development of a Biopharmaceu-tics Drug Disposition Classification System. Pharm. Res. 22 11-23... 

Wu, C.Z. and Benet, L.Z. (2005) Predicting drug disposition via application of BCS transport/absorption/elimination interplay and development of a biopharmaceutics drug disposition classification system. Pharmaceutical Research, 22, 11-23. 

Kim RB. Organic anion-transporting polypeptide (OATP) transporter family and drug disposition. Eur J Clin Invest 2003 33(suppl 2) 1-5. 

You G. The role of organic ion transporters in drug disposition an update. Curr Drug Metab. 2004 5 ... 

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