天津市新药安全评价研究中心LOGO
释药技术与药代动力学国家重点实验室
天津药物研究院

Drug transporter, as transmembrane protein, play an important role in the adsorption, distribution and elimination of a wide variety of drugs. Transporter mediated drug-drug interactions can lead to changed systemic exposure, resulting in variations in drug response of the co-administered drugs. Therefore, it is important to evaluate potential drug interactions prior to market approval as well as during the post-marketing period.

 

Which transporters are important for drug development and should be    considered for evaluation during drug development?

 

 

 

Customized transporter assay service upon requests :

Pharmacokinetics evaluation by drug transporters

Absoption: time dependent, Km and Vmax

Distribution: time dependent, Km and Vmax

Metabolism: time dependent, Km and Vmax

Elimination: time dependent, Km and Vmax

Transporter-mediated drug-drug interaction (DDI)

Inhibition studies: IC50 and Ki

Cell model for transporter-mediated DDI

Inside-out vesicles for transporter-mediated DDI

 

Targeting drug screening studies

Amino acid transporter 1 (LAT1)

Sodium-dependent glucose transporter (SGLT)

Uric acid transporter 1 (URAT1)

 

In vitro transporter assay

Uptake and Efflux Studies

Monolayer Transport Studies: efflux

Surrogate Transporter Activity: ATPase studies (Pi)

 

Cell model for transporter study

Transporters

Standard substrates

Inhibitors

 

 

 

 

 

 

 

 

OAT1$

14C-paraaminohippuric acid (PAH)

probenecid

OAT2

3H-prostaglandin F2α (PGF2α)

 

OAT3$

3H-estrone sulfate

probenecid

OAT4

3H-estrone sulfate

probenecid

OAT7

3H-estrone sulfate

 

OCT1 wild

14C-tetraethylammonium (TEA)

cimetidine

OCT1

14C-tetraethylammonium (TEA)

cimetidine

OCT2-a$

14C-tetraethylammonium (TEA)

cimetidine

OCT2-b$

14C-tetraethylammonium (TEA)

cimetidine

OCT3

3H-histamine

cimetidine

MDR1 (p-gp) $

3H-digoxin

 

PEPT1

3H-glycylsarcosine

 

PEPT2

3H-glycylsarcosine

 

URAT1

14C-uric acid

 

OCTN1

14C-tetraethylammonium (TEA)

 

OCTN2

3H-L-carnitine

 

OATP1B1 (OATP2) $

3H-estrone sulfate

 

OATP1B3 (OATP8)* $

3H-Estradiol-17beta-D-glucuronide

 

OATP2B1 (OATP-B)

3H-estrone sulfate

 

LAT1

14C-1-leucin

 

LAT2

14C-L-leucin

 

SGLT1*

14C-glucose

 

SGLT2*

14C-glucose

 

 

 

 

 

 

 

MDR1/P-gp$

3H-digoxin

 

MRP1 (ABCC1)

3H- leukotriene C4

 

MRP2 (ABCC2)

3H-Estradiol-17beta-D-glucuronide

 

MRP3 (ABCC3)

3H-Estradiol-17beta-D-glucuronide

 

MRP4 (ABCC4)

3H-DHEAS

 

MRP5 (ABCC5)

3H-cGMP

 

BCRP (ABCG2) $

3H-estrone sulfate

 

BSEP (ABCB11)

3H-Taurocholate

 

$ Clinically important transporters recomended by International Transporter Consortium (ITC)

* Cell line is in cloning

 

 

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