1. CYP450 The Key of Drug-Interaction
내분비 내과
황보 영

2. Definition Cytochrome ? 세포색소, 헴단백질 일종 Cytochrome P450?
내인성 혹은 외인성 물질의 산화적 대사에 관여함으로써 이들 물질이 소변이나 담즙으로 쉽게 배설될 수 있도록 친수성 물질로 전환시키는 heme을 함유한 효소군

4. Classification

5. Endoplasmic reticulum Steroid, bile acid, cholesterol
Classification
Endoplasmic reticulum
Toxin, Carcinogen, Drug
Mitochondira
Steroid, bile acid, cholesterol

6. Drug Metabolism

7. Phases of Drug Metabolism
Phase I Reactions
Convert compound into a more polar (=hydrophilic) metabolite by adding functional groups (-OH, -SH, -NH2, -COOH, etc.)
Often these metabolites are inactive
May be sufficiently polar to be excreted readily
Phase II Reactions
Conjugation with endogenous substrate to further increase aqueous solubility
Conjugation with glucuronide, sulfate, acetate, amino acid

8. Phases of Drug Metabolism

9. Drug metabolism & CYP450 CYP450 metabolism Major Site : Liver
2nd site : Enterocyte
in the epithelium of
small intestine

11. Induction of CYP3A4-Mediated Metabolism
N Engl J Med 2005;352:

13. Consequences of Inhibition of First-pass metabolism

23. New FDA Labeling Changes for Simvastatin
The risk of myopathy & rhabdomyolysis is increased by concomitant use of simvastatin and:
Potent inhibitors of CYP3A4
-Should be avoided or simvastatin therapy suspended
Fibrates or niacin
-Should be avoided or do not exceed simvastatin 10mg/day
Amiodarone or verapamil (other 3A4 inhibitors)
-Do not exceed simvastatin 20mg/day

24. SSRI Selective Serotonin Reuptake Inhibitors : antidpressant
treatment of choice of major depression
Fluoxetine (Prozac, 1988)
It’s usefullness
:Because of benign side effects
Minimal quinidine-like property
Low anticholinergic effect
Lack of effects on blood pressure

26. Case Application

27. CYP Inhibition by SSRI
From Stahl (2000) Essential Psychopharmacology

28. CYP Inhibition by SSRI

30. Drug Interaction
Cytochrome P450