薬物相互作用(3)

ゲノム薬理と薬物相互作用

小　澤　正　吾*
　　　　　　　　　　　　　　　　　　　　　　
Drug-Drug Interaction in Pharmacogenetics and Pharmacogenomics

Shogo OZAWA*

Drug metabolism and excretion is composed of four steps : Absorption, distribution, metabolism and excretion. The four steps are often abbreviated as ADME. Drug-drug interaction may occur at each step of ADME. Reported examples of drug-drug interaction occur mainly at the level of "drug metabolizing enzymes(DME)". The mechanisms of drug-drug interaction are : 1)Competitive inhibition of DME, 2)Destruction or irreversible inhibition of DME, 3)Induction of DME. Co-administration of 5-fluorouracil and sorivudine resulted in severe gastrointestinal and bone marrow toxicities. The toxicity is due to irreversible inhibition of dihydropyrimidine dehydrogenase by a sorivudine metabolite, which plays a role in detoxification of 5-fluorouracil.
However, there is an example of beneficial drug-drug interaction, where proton pump inhibitor, omep-razole, antibiotics, amoxicillin and clarithromycin, are co-administered for eradication of Helicobacter pylori. Omeprazole is metabolized by CYP2C19 and CYP3A4. In poor metabolizers of omeprazole, a higher area under the drug concentration curve(AUC) and higher efficacy are achieved as compared to extensive metabolizers of omeprazole. In this regimen, co-administration of clarithromycin which is metabolized by CYP3A4 effectively raises the AUC of omeprazole. Thus, this drug combination results in a beneficial drug-drug interaction.
[Rinsho Byori 50 : 146〜150, 2002]

*Division of Pharmacology, National Institute of Health Sciences, Setagaya, Tokyo 158-8501

【Key Words】drug-drug interaction(薬物相互作用)，drug metabolizing enzymes(薬物代謝酵素)，pharma-cogenetics(薬理遺伝学)，pharmacogenomics(ゲノム薬理学)

*国立医薬品食品衛生研究所 薬理部(〒158-8501 東京都世田谷区上用賀1-18-1)