Subject(s)
Humans , Male , Female , Aged , Aged, 80 and over , Clarithromycin/adverse effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Cytochrome P-450 CYP3A Inhibitors/adverse effects , Pyrimidines/metabolism , Pyrimidines/therapeutic use , Pyrimidines/pharmacokinetics , Rhabdomyolysis/chemically induced , Sulfonamides/metabolism , Sulfonamides/therapeutic use , Sulfonamides/pharmacokinetics , Fatty Acids, Monounsaturated/metabolism , Fatty Acids, Monounsaturated/therapeutic use , Fatty Acids, Monounsaturated/pharmacokinetics , Pravastatin/metabolism , Pravastatin/therapeutic use , Pravastatin/pharmacokinetics , Hydroxymethylglutaryl-CoA Reductase Inhibitors/metabolism , Organic Anion Transporters , Organic Anion Transporters, Sodium-Independent/antagonists & inhibitors , Liver-Specific Organic Anion Transporter 1 , Drug Interactions , Acute Kidney Injury/chemically induced , Rosuvastatin Calcium , Fluorobenzenes/metabolism , Fluorobenzenes/therapeutic use , Fluorobenzenes/pharmacokinetics , Solute Carrier Organic Anion Transporter Family Member 1B3 , Fluvastatin , Hyperkalemia/chemically induced , Indoles/metabolism , Indoles/therapeutic use , Indoles/pharmacokineticsABSTRACT
OATP1B3, a member of SLC superfamily, is specifically expressed on the sinusoidal membrane of hepatocytes and is considered to be important in hepatic drug elimination. The overexpression of OATP1B3 was found recently in tumor tissues such as prostate, colon, and pancreatic tumors. Sequence variations in SLCO1B3 gene, such as SNPs, have been described and a common haplotype consisting of 334T>G and 699G>A SNPs is related to altered transport characteristics of OATP1B3. OATP1B3 is of relevance to drug metabolism through affecting alteration of hepatic concentration of endo- and xenobiotic compounds that interact with nuclear receptors such as PXR and CAR, and thereby directly alter the extent of target gene transcription, including major CYP isoenzymes such as CYP3A4. This review will provide an overview of substrates and inhibitors of OATP1B3 and subsequently to assess the effect of genetic mutation on transport activity. The studies linking OATP1B3 with cancer clinical outcomes are also discussed in this review.