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Book Chapter

Affinity of Drugs to the Different Renal Transporters for Organic Anions and Organic Cations


Ullrich,  Karl Julius
Emeritusgroup Physiology, Max Planck Institute of Biophysics, Max Planck Society;

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Ullrich, K. J. (2002). Affinity of Drugs to the Different Renal Transporters for Organic Anions and Organic Cations. In G. L. Amidon, & W. Sadée (Eds.), Pharmaceutical Biotechnology (pp. 159-179). Springer, Boston, MA: Kluwer Academic Publishers 2002.

Cite as: http://hdl.handle.net/21.11116/0000-0007-201B-7
Drugs are taken up into the body by different routes and are excreted by the kidney or by the liver, either directly or after metabolic transformation. Discriminating between renal and extrarenal clearance of drugs and their metabolites is fruitful, and tables containing quantitative clearance data are of value (Dettli, 1996). In the past two decades, renal drug excretion has been studied mainly on two levels: (1) via transporters for organic anions and for organic cations, and (2) localization of the transport processes at the contraluminal or luminal cell side of the proximal tubule. These results were achieved by kinetic transport studies using either the tubule in situ (Ullrich and Rumrich, 1990) or membrane vesicles from either side of the cell (Kinne-Saffran and Kinne, 1990). Our present knowledge of the respective transport mechanisms has been aided by the cloning and functional expression of the main transporters (Gründemann et al., 1994; Sekine et al., 1997; Wolff et al., 1997; Sweet et al., 1997; Zhang et al., 1997a) and by the evaluation of their substrate specificity. These topics are discussed in the proceedings of a recent symposium (Fleck et al., 1998) and by Chapters 15 and 16 in this book. One is often faced with the question of whether a drug interacts with a certain transporter and what transport interactions with other drugs have to be expected. Fortunately, a large body of data is available to answer this question. A list of Ki values of drugs can be established, and the reciprocal of these Ki values can be considered as a reliable measure for the relative affinities of drugs for the respective transporters under in situ conditions. The data presented in this chapter were obtained on the rat proximal tubule in situ with the same micropuncture technique for the luminal as for the contraluminal cell side, so that all data can be compared quantitatively. For these transport studies appropriate test substances were chosen and the transporters named according to these test substances: para-aminohippurate (PAH), sulfate, and succinate as representative anions; N¹-methyl-nicotinamide (NMeN+), tetraethylammonium (TEA+), methyl-phenyl-pyridinium (MPP+), and choline+ as representative cations.