OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine.

Article Details

Citation

Cvetkovic M, Leake B, Fromm MF, Wilkinson GR, Kim RB

OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine.

Drug Metab Dispos. 1999 Aug;27(8):866-71.

PubMed ID
10421612 [ View in PubMed
]
Abstract

Fexofenadine, a nonsedating antihistamine, does not undergo significant metabolic biotransformation. Accordingly, it was hypothesized that uptake and efflux transporters could be importantly involved in the drug's disposition. Utilizing a recombinant vaccinia expression system, members of the organic anion transporting polypeptide family, such as the human organic anion transporting polypeptide (OATP) and rat organic anion transporting polypeptides 1 and 2 (Oatp1 and Oatp2), were found to mediate [(14)C]fexofenadine cellular uptake. On the other hand, the bile acid transporter human sodium taurocholate cotransporting polypeptide (NTCP) and the rat organic cation transporter rOCT1 did not exhibit such activity. P-glycoprotein (P-gp) was identified as a fexofenadine efflux transporter, using the LLC-PK1 cell, a polarized epithelial cell line lacking P-gp, and the derivative cell line (L-MDR1), which overexpresses P-gp. In addition, oral and i.v. administration of [(14)C]fexofenadine to mice lacking mdr1a-encoded P-gp resulted in 5- and 9-fold increases in the drug's plasma and brain levels, respectively, compared with wild-type mice. Also, a number of drug inhibitors of P-gp were found to be effective inhibitors of OATP. Because OATP transporters and P-gp colocalize in organs of importance to drug disposition such as the liver, their activity provides an explanation for the heretofore unknown mechanism(s) responsible for fexofenadine's disposition and suggests potentially similar roles in the disposition of other xenobiotics.

DrugBank Data that Cites this Article

Drug Transporters
DrugTransporterKindOrganismPharmacological ActionActions
FexofenadineP-glycoprotein 1ProteinHumans
Unknown
Substrate
Details
FexofenadineSolute carrier organic anion transporter family member 1A2ProteinHumans
Unknown
Substrate
Details
FexofenadineSolute carrier organic anion transporter family member 1B1ProteinHumans
Unknown
Substrate
Details
IndinavirSolute carrier organic anion transporter family member 1A2ProteinHumans
Unknown
Inhibitor
Details
LovastatinSolute carrier organic anion transporter family member 1A2ProteinHumans
Unknown
Inhibitor
Details
NelfinavirSolute carrier organic anion transporter family member 1A2ProteinHumans
Unknown
Inhibitor
Details
QuinidineSolute carrier organic anion transporter family member 1A2ProteinHumans
Unknown
Inhibitor
Details
RitonavirSolute carrier organic anion transporter family member 1A2ProteinHumans
Unknown
Inhibitor
Details
SaquinavirSolute carrier organic anion transporter family member 1A2ProteinHumans
Unknown
Inhibitor
Details
VerapamilSolute carrier organic anion transporter family member 1A2ProteinHumans
Unknown
Inhibitor
Details