What are OATP1B1 inhibitors?

OATP1B1 and OATP1B3 are transporters that are expressed on the sinusoidal membrane of hepatocytes; they accept a number of therapeutic reagents as their substrates. In vitro and in vivo studies have shown that some drugs inhibit these transporters and cause clinically relevant drug-drug interactions (DDIs).

What does organic anion transporter do?

Organic anion transporters (OATs) are the secondary/tertiary active transporter proteins that regulate anion balance in the body. They are primarily expressed in the kidney and liver and control the excretion of common drugs, toxins, and endogenous metabolites into the urine.

What is the SLCO1B1 gene?

The SLCO1B1 gene provides instructions for making a protein called organic anion transporting polypeptide 1B1, or OATP1B1. This protein is found in liver cells; it transports compounds from the blood into the liver so that they can be cleared from the body.

Where are OATPs located?

OATPs are encoded by genes of the SLCO family (previously SLC21) (Hagenbuch and Meier, 2004). The genes encoding human OATP1 family members are located in the short arm of chromosome 12, whereas genes encoding other OATPs are located in chromosomes 3, 5, 8, 11, 15 and 20.

What is the likely consequence of inhibiting the OATP1B1 mediated transport of an OATP1B1 substrate?

Inhibition of OATPs can lead to defective elimination, result in sudden increases in plasma concentration and area under the curve (AUC) for drugs that are substrates of these transporters [36], and ultimately increase the risk of therapy-related side effects.

Where is OATP1B1 found?

hepatocytes
OATP1B1 is located to the sinusoidal (basolateral) membrane of hepatocytes, and is expressed uniformly throughout the lobules. Despite its name, OATP1B1 has broad substrate selectivity that includes anionic, zwitterionic, and neutral lipophilic drugs.

What is oat inhibitor?

OAT Products Lesinurad (RDEA-594) is a selective uric acid reabsorption inhibitor (SURI) under investigation for treatment of gout in combination with xanthine oxidase inhibitors.

What drug competes for organic anion transport in the kidney?

Other OAs can compete with diuretics for transport by OAT. These include β-lactam and sulfonamide antibiotics, nonsteroidal anti-inflammatory drugs,48 antiviral agents such as adefovir, p-aminohippurate, methotrexate, uric acid, and a number of endogenous organic anions.

What is SLCO1B1 drug transport?

SLCO1B1 (solute carrier organic anion transporter family member 1B1) is a drug transporter that helps the body get rid of certain medicines through the liver. There are many medications that may be affected by SLCO1B1. There are many variations or genetic differences in the gene for SLCO1B1.

What is SLCO1B1 decreased function?

Having SLCO1B1 decreased function means that you may have reduced transport of certain medications into the liver for processing and removal from the body. This may lead to slightly higher than normal medication levels in the body, or have no noticeable effects.

What is the likely consequence of inhibiting the oatp1b1 mediated transport of an oatp1b1 substrate?

What is Bcrp substrate?

BCRP SUBSTRATES Substrates of BCRP initially were reported to be a wide range of chemotherapeutics such as mitoxantrone, camptothecin derivates, flavopiridol, and methotrexate (1). Notably, several TKIs such as imatinib, gefitinib, and nilotinib are BCRP substrates (1,13).

What does SLCO1B1 stand for?

What is oat1 b1 inhibitors?

A medication used to treat gouty arthritis, tophaceous gout, and hyperuricemia. An antibiotic used to treat several types of mycobacterial infections including Mycobacterium avium complex, leprosy, and in combination with other antibacterials to treat latent or active tuberculosis.

What is PGP substrate?

Substrates of P-glycoprotein are susceptible to changes in pharmacokinetics due to drug interactions with P-gp inhibitors or inducers. Some of these substrates include colchicine, ciclosporin, dabigatran, digoxin, diltiazem, fexofenadine, indinavir, morphine, and sirolimus.

Why probenecid is used along with penicillin?

Probenecid is also used in combination with penicillin and penicillin derivatives (such as ampicillin and nafcillin) to prolong their plasma half-life and increase serum concentrations. The typical dose for this effect is 1 g daily.

What is renal organic cation transporter?

Abstract. In the kidney, human organic cation transporters (OCTs) and multidrug and toxin extrusion proteins (MATEs) are the major transporters for the secretion of cationic drugs into the urine.

Which drugs are affected by SLCO1B1?

The gene organic anion transporting polypeptide 1B1 (OATP1B1, also known as SLCO1B1) encodes the transmembrane protein OATP1B1, which transports anionic drugs such as statins, irinotecan, rifampin, repaglinide and methotrexate.

What drugs use SLCO1B1 drug transport?

What is BCRP inhibitor?

BCRP inhibitors include, among others, fumitremorgin C (FTC), the FTC analogue Ko143, the acridone carboxamide derivative GF120918, anti-HIV protease inhibitors nelfinavir and ritonavir, the dietary flavonoids chrysin and biochanin A, the tyrosine kinase inhibitors gefitinib and imatinib [5, 16, 36], and herb extracts …

What is the function of OATP1B1 and OATP1B3?

OATP1B1 and OATP1B3 are transporters that are expressed on the sinusoidal membrane of hepatocytes; they accept a number of therapeutic reagents as their substrates. In vitro and in vivo studies have shown that some drugs inhibit these transporters and cause clinically relevant drug-drug interactions (DDIs).

Does oatp1b transporter inhibition affect the pharmacokinetics of atorvastatin?

effect of OATP1B transporter inhibition on the pharmacokinetics of atorvastatin in healthy volunteers The inhibition of hepatic uptake transporters, such as OATP1B1, on the pharmacokinetics of atorvastatin is unknown.

What is the role of OATP1B1 in hepatic hepatic hmme uptake?

We confirmed that OATP1B1, rather than OATP2B1, is the major transporter involved in hepatic HMME uptake, which is consistent with our hypothesis. Thus, the greater uptake of HMME-2 mediated by OATP1B1 could potentially lead to a lower systemic exposure of HMME-2, compared with HMME-1, in humans.

Which OATP transporters are involved in drug transport?

Of the 11 human OATP transporters, OATP1B1, OATP1B3 and OATP2B1 are expressed on the sinusoidal membrane of hepatocytes and can facilitate the liver uptake of their substrate drugs. OATP1A2 is expressed on the luminal membrane of small intestinal enterocytes and at the blood-brain barrier, potentially mediating drug transport at these sites.