Drug Metabolism in Drug Design and Development Basic Concepts and Practice

TABLE 6.1 Tissue distribution and substrate properties of major ABC and SLC transporters.Gene

Protein name Tissue distribution

Substrate properties

Selected inhibitor

and (inducer)

Driving force

ABC transportersABCB1

MDR1, P-

glycoprotein

Intestine, liver, kidney,

brain, placenta,adrenal, testes,cancer cells

Lipophilic, amphiphilic

with weak organic cation,containing hydrogen bonddonor and acceptor, such asdigoxin, talinolol, vinblastine,paclitaxel, fexofenadine,quinidine, loperamide,topotecan, gleevec,colchicines,daunorubicin, Calceine-AM,Rhodamine123

ritonavir, ketoconazole,

cyclosporine, verapamil,erythromycin, quinidine,PSC833, GF918120,LY335979 (rifampin,St John’s wort)

Intrinsic ATPase

activity andATP hydrolysis

ABCB11

BSEP, SPGP Liver

Bile salts and paclitaxel

All major bile salts, CsA,

bosentan

Intrinsic ATPase

activity andATP hydrolysis

ABCC1

MRP1

Ubiquitous (mainly

in lung, kidney,brain, colon, testis,peripheral bloodmononuclear cells),cancer cells

Glutathione, glucuronide and

sulfate conjugates.Hydrophilic with organicanion. Substrates overlapbetween MRP1, MRP2,and MRP3, such as calcein,LTC

, methotrexate, and 4

vinblastine.

Probenecid, indomethacin,

MK571, cyclosporine A(chlorambucil, epirubicin)

Intrinsic ATPase

activity andATP hydrolysis

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