Liver Intestine

Normal heme transport during maturation of erythrocytes

Excretion of phospholipids into bile Excretion of bile salts into bile

Excretion of plant sterols into bile and intestinal lumen

Anticancer drugs: etoposide, methotrexate

Glutathione conjugates: LTC4, glutathione conjugate of 15-deoxy-delta prostaglandin J2

Glucuronide conjugates: estradiol-17-D-glucuronide, etoposide glucuronide Sulfate conjugates of bile salts: taurolithocholate sulfate Bile salts: glycocholate, taurocholate Others: folate, leucovorin Characteristics: Nucleotide analogues Anticancer drugs: 6-mercaptopurine, methotrexate Glucuronide conjugates: estradiol-17-D-glucuronide Cyclic nucleotides: cyclic AMP, cyclic GMP HIV protease inhibitors: adefovir Others: folate, leucovorin, taurocholate (with GSH) Characteristics: Nucleotide analogues Anticancer drugs: 6-mercaptopurine Cyclic nucleotides: cyclic AMP, cyclic GMP HIV protease inhibitors: adefovir Anticancer drugs: doxorubicin*, etoposide* Glutathione conjugate of: LTC4 Other: BQ-123 (cyclic peptide ET-1 antagonist) Anticancer drugs: methotrexate, mitoxantrone, camptothecin analogs (SN-38, etc.), topotecan Glucuronide conjugates: 4-methylumbelliferone glucuronide, estradiol-17-D-glucuronide Sulfate conjugates: dehydroepiandrosterone sulfate, estrone-3-sulfate Others: cholesterol, estradiol Characteristics: Phospholipids

Characteristics: Bile salts

Characteristics: Plant sterols

NOTE: Representative substrates and cytotoxic drugs with increased resistance (*) are included in this table (cytotoxicity with increased resistance is usually caused by the decreased accumulation of the drugs). Although MDR3 (ABCB4), BSEP (ABCB11), ABCG5, and ABCG8 are not directly involved in drug disposition, inhibition of these physiologically important ABC transporters will lead to unfavorable side effects.

Little clinically applicable information regarding MRP2 and BCRP drug-handling is available. Most MRP2 or BCRP substrates also can be transported by the OATP family transporters on the sinusoidal membrane.

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