Drug transport

DRUG TRANSPORTPREPARED BY :

NUR DIANA BT MOHAMED NOOR(0316808)

Learning Outcome :

Importance of drug transporter

Types of drug transporter

Function and mechanism of P-glycoprotein

Clinical importance of P-glycoprotein

Importance of Drug

Transporter

Role in overall disposition of drugs to the

target organs

Significant determinant of drug-drug

interaction

Variability in drug response

Types of drug transporter

Two types of transporter :

ATP binding Cassette (ABC) – Found in ABCB, ABCD and ABCG family. Associated with multidrug resistance (MDR) of tumor cells causing treatment failure in cancer.

Solute Carrier (SLC) – Transport varieties of solute include both charged or uncharged

Comparison ATP Binding Cassette Solute Carrier

Efflux transporter Influx / bidirectionaltransporter

Utilize energy from ATP Electrochemical gradient / facilitated diffusion

Primary active Secondary active

Subfamilies : ABCA, ABCB, ABCD, ABCE, ABCDF, ABCG

Subfamilies ; SLC15, SLC22, SLCO

P-glycoprotein

• ATP binding cassette sub family B member-

1 (ABCB 1)

• Multidrug resistance protein 1 (MDR1)

• Transport various molecules, including

xenobiotic, across cell membrane

• Extensively distributed and expressed

throughout the body

Function of P-glycoprotein

Site of transportation Function

Liver – Bile Elimination

Kidney - Urine Excretion

Placenta – Maternal blood Protect fetal from drug exposure

Intestine – Intestinal lumen Reduce drug absorption into the blood

Brain – Blood Monitor drug access to the brain

Mechanism of P-glycoprotein

① Substrate bind to P-gp form the inner

leaflet of the membrane

② ATP binds at the inner side of the

protein

③ ATP is hydrolyzed to produce ADP and

energy

④ Substrate is excreted outside the cell

Clinical Importance

P-gp is a multidrug resistant protein (MDR)

Role of P-gp is significant in tumor cells.

Expression of P-gp in tumor cells reduces the

accessibility of cytotoxic drugs by eliminating them

in various pathways. Hence, P-gp may act as a

major barrier to effective drug treatments.

Over expression of P-gp in limit the treatment for

cancer, AIDS, Alzheimer’s and epilepsy.

References

Dean M, Hamon Y, Chimini G (July 2001). "The human ATP-binding cassette (ABC) transporter superfamily”

Hediger MA, Romero MF, Peng JB, Rolfs A, Takanaga H, Bruford EA (2004). "The ABCs of solute carriers: physiological, pathological and therapeutic implications of human membrane transport proteins: Introduction”

Dean, Michael (2002-11-01). "The Human ATP-Binding Cassette (ABC) Transporter Superfamily”

Peter N Bennett, Morris J Brown, Pankaj Sharma, 11th Edition (2012). “Clinical Pharmacology”

Department of Drug Metabolism, Merck Research Laboratories (Nov 2003). “Clinical relevance of P-glycoprotein in drug therapy”

Thank You