Organic anion transporters: discovery, pharmacology, regulation and roles in pathophysiology.

Article Details

Citation

VanWert AL, Gionfriddo MR, Sweet DH

Organic anion transporters: discovery, pharmacology, regulation and roles in pathophysiology.

Biopharm Drug Dispos. 2010 Jan;31(1):1-71. doi: 10.1002/bdd.693.

PubMed ID
19953504 [ View in PubMed
]
Abstract

Our understanding of the mechanisms behind inter- and intra-patient variability in drug response is inadequate. Advances in the cytochrome P450 drug metabolizing enzyme field have been remarkable, but those in the drug transporter field have trailed behind. Currently, however, interest in carrier-mediated disposition of pharmacotherapeutics is on a substantial uprise. This is exemplified by the 2006 FDA guidance statement directed to the pharmaceutical industry. The guidance recommended that industry ascertain whether novel drug entities interact with transporters. This suggestion likely stems from the observation that several novel cloned transporters contribute significantly to the disposition of various approved drugs. Many drugs bear anionic functional groups, and thus interact with organic anion transporters (OATs). Collectively, these transporters are nearly ubiquitously expressed in barrier epithelia. Moreover, several reports indicate that OATs are subject to diverse forms of regulation, much like drug metabolizing enzymes and receptors. Thus, critical to furthering our understanding of patient- and condition-specific responses to pharmacotherapy is the complete characterization of OAT interactions with drugs and regulatory factors. This review provides the reader with a comprehensive account of the function and substrate profile of cloned OATs. In addition, a major focus of this review is on the regulation of OATs including the impact of transcriptional and epigenetic factors, phosphorylation, hormones and gender.

DrugBank Data that Cites this Article

Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
AlprostadilSolute carrier family 22 member 6ProteinHumans
Unknown
Substrate
Inhibitor
Details
Betamethasone phosphateSolute carrier family 22 member 8ProteinHumans
Unknown
Substrate
Details
BudesonideSolute carrier family 22 member 8ProteinHumans
Unknown
Substrate
Details
BumetanideSolute carrier family 22 member 6ProteinHumans
Unknown
Substrate
Inhibitor
Details
CaptoprilSolute carrier family 22 member 6ProteinHumans
Unknown
Substrate
Inhibitor
Details
CefaclorSolute carrier family 22 member 8ProteinHumans
Unknown
Substrate
Inhibitor
Details
CefaloridineSolute carrier family 22 member 6ProteinHumans
Unknown
Substrate
Details
CefaloridineSolute carrier family 22 member 8ProteinHumans
Unknown
Substrate
Inhibitor
Details
CefotiamSolute carrier family 22 member 6ProteinHumans
Unknown
Substrate
Inhibitor
Details
CefotiamSolute carrier family 22 member 8ProteinHumans
Unknown
Substrate
Inhibitor
Details
CeftibutenSolute carrier family 22 member 6ProteinHumans
Unknown
Substrate
Details
CeftibutenSolute carrier family 22 member 8ProteinHumans
Unknown
Substrate
Inhibitor
Details
CeftizoximeSolute carrier family 22 member 6ProteinHumans
Unknown
Substrate
Inhibitor
Details
CeftizoximeSolute carrier family 22 member 8ProteinHumans
Unknown
Substrate
Inhibitor
Details
Cholic AcidSolute carrier family 22 member 8ProteinHumans
Unknown
Substrate
Inhibitor
Details
CitrullineSolute carrier family 22 member 6ProteinHumans
Unknown
Substrate
Details
Cortisone acetateSolute carrier family 22 member 8ProteinHumans
Unknown
Substrate
Details
DexamethasoneSolute carrier family 22 member 8ProteinHumans
Unknown
Substrate
Details
Dexamethasone acetateSolute carrier family 22 member 8ProteinHumans
Unknown
Substrate
Details
EdaravoneSolute carrier family 22 member 6ProteinHumans
Unknown
Substrate
Details
EdaravoneSolute carrier family 22 member 8ProteinHumans
Unknown
Substrate
Details
Ellagic acidSolute carrier family 22 member 6ProteinHumans
Unknown
Substrate
Inhibitor
Details
FexofenadineSolute carrier family 22 member 8ProteinHumans
Unknown
Substrate
Details
FluoresceinSolute carrier family 22 member 6ProteinHumans
Unknown
Substrate
Inhibitor
Details
HydrocortisoneSolute carrier family 22 member 8ProteinHumans
Unknown
Substrate
Details
Hydrocortisone aceponateSolute carrier family 22 member 8ProteinHumans
Unknown
Not AvailableDetails
Hydrocortisone acetateSolute carrier family 22 member 8ProteinHumans
Unknown
Not AvailableDetails
Hydrocortisone butyrateSolute carrier family 22 member 8ProteinHumans
Unknown
Not AvailableDetails
Hydrocortisone cypionateSolute carrier family 22 member 8ProteinHumans
Unknown
Not AvailableDetails
Hydrocortisone phosphateSolute carrier family 22 member 8ProteinHumans
Unknown
Not AvailableDetails
Hydrocortisone probutateSolute carrier family 22 member 8ProteinHumans
Unknown
Not AvailableDetails
Hydrocortisone valerateSolute carrier family 22 member 8ProteinHumans
Unknown
Not AvailableDetails
IndomethacinSolute carrier family 22 member 6ProteinHumans
Unknown
Substrate
Inhibitor
Details
LeucovorinSolute carrier family 22 member 8ProteinHumans
Unknown
Substrate
Inhibitor
Details
MedrysoneSolute carrier family 22 member 8ProteinHumans
Unknown
Substrate
Details
Prednisolone phosphateSolute carrier family 22 member 8ProteinHumans
Unknown
Substrate
Details
QuinaprilSolute carrier family 22 member 8ProteinHumans
Unknown
Substrate
Details
RosuvastatinSolute carrier family 22 member 8ProteinHumans
Unknown
Substrate
Inhibitor
Details
SilibininSolute carrier family 22 member 6ProteinHumans
Unknown
Substrate
Inhibitor
Details
SitagliptinSolute carrier family 22 member 8ProteinHumans
Unknown
Substrate
Details
TetracyclineSolute carrier family 22 member 8ProteinHumans
Unknown
Substrate
Inhibitor
Details
TrifluridineSolute carrier family 22 member 6ProteinHumans
Unknown
Substrate
Inhibitor
Details
ZalcitabineSolute carrier family 22 member 6ProteinHumans
Unknown
Substrate
Details
ZidovudineSolute carrier family 22 member 6ProteinHumans
Unknown
Substrate
Details
ZidovudineSolute carrier family 22 member 8ProteinHumans
Unknown
Substrate
Inhibitor
Details