Drug Metabolism in Drug Design and Development Basic Concepts and Practice

TABLE 6.1 (

Continued

)

Gene

Protein name Tissue distribution

Substrate properties

Selected inhibitor

and (inducer)

Driving force

SLC21A9/

SLCO2B1

OATP-B,

OATP-RP2,OATP2B1

Liver, intestine,

pancreas, lung,ovary, testes, spleen

SLC21A11/

SLCO3A1

OATP-D,

OATP3A1

Ubiquitous (strong

expression inleukocytes spleen),cancer cells

SLC21A12/

SLCO4A1

OATP-E,

OATP-RP1,OATP4A1

Ubiquitous (mainly

in skeletal muscles),cancer cells

SLC22A1

OCT1

Liver

Small organic cationsTetraethylmethylammonium

(TEA), MPP

+

, metformin,

azidothymine (AZT),choline

Tetraethylmethylammonium,

cimetidine, and HIVinhibitors

SLC22A2

OCT2

Kidney, brain

OCT2 is driven

by membranepotential

SLC22A3

OCT3, EMT Skeletal muscle,

liver, placenta,kidney, heart

Small organic cationsTEA, dopamine,

guanidine

SLC22A4

OCTN1

Kidney, skeletal

muscle, prostate,placenta, heart

Small organic cations

TEA, verapamil,

imipramine,nicotine, procainamide

OCTN1 is driven

by H

+

144