6

Question 1

P-glycoprotein

Answer 1

● Coded by ABCB1
● Protection from endogenous and exogenous toxins
● Important in determining absorption and distribution of drugs
● Can cause drug resistance in tumor cells
● Efflux in intestine and BBB
- Influx into bile duct and nephron
● Polymorphisms are significant, especially in low therapeutic range drugs
○ Ex: digoxin

Question 2

ABCB1 PK

Answer 2

Question 3

OATP

Answer 3

● Coded by SLCO
● Transporter for large endogenous and exogenous substrates
● Drug substrates include statins

Question 4

Statins

Answer 4

● Hyperlipidemia medication
● 2-fold increase in AUC observed in Asian patients
● Metabolism is complex, but we’ll focus on 3 proteins
○ OATP1B1 (SLCO1B1) - influx transporter to liver
○ ABCG2 - efflux in intestine
○ CYP2C9 - metabolizes most statins

Question 5

OATP1B1 PK

Answer 5

Question 6

ABCG2

Answer 6

Question 7

CYP2C9 PK

Answer 7

Question 8

Pharmacogenomic Impact

Answer 8

● Guidelines exist for prescribing statins based on SLCO1B1 genotype
● If SLCO1B1 is not genotyped, start Asian patients on lower doses
● However, this is complicated by many factors
○ Definitions of race
○ Many enzymes involved than just these 3
○ Weighing different combinations of polymorphisms
○ Conflicting data