Study On The Age-Related Changes In The Activities Of Drug Metabolizing Enzymes: Cyp2D6 And N-Acetyltransferase

약물대사효소 CYP2D6와 N-acetyltransferase 활성의 고령화에 따른 변화에 관한 연구

Background : The effect of age on the activity of drug metabolizing enzymes has not been studied thoroughly. We examined the effect of age on the metabolic activity of CYP2D6 and N-acetyltransferase. Methods : Metoprolol and isoniazid were used as probe drugs of CYP2D6 and N-acetyltransferase, respectively. We measured metabolic ratios of metoprolol and isoniazid in 80 subjects of $21{\sim}85$ years old. Metabolic ratio(MR) of metoprolol was defined as the ratio of $metoprolol/{\alpha}-hydroxymetoprolol$ in the urine collected for 8 hours after the administration. Isoniazid/acetylisoniazid was used for MR of isoniazid. Concentrations of parent drug and metabolite were assayed by HPLC simultaneously. General linear model in SAS $8.1^{\circledR}$ was used for the statistical analysis 따ter visual exploration. Metabolic ratios were log-transformed to be normalized for analysis. Results : Demographic characteristics were similar between groups of metabolic activities. MRs of both drugs were not significantly different betweeb groups by age, sex and smoking. Mean MR of metoprolol for adult group(age<65) was 0.85$(90%\;CI:\;0.48{\sim}1.48)$ times that of elderly group$(age{\geq}65)$ and mean MR of isoniazid for adult group was 1.01$(90%\;CI:\;0.57{\sim}1.79)$ times that of elderly group. The proportions of poor metabolizer(adult: elderly=1.75%: 0 %) or slow acetylator(adult: elderly=17.54%: 17.39%) were not different between age groups. The effect of age on the metabolism was not significant even when it was adjusted with phenotype(p-value=0.58 and 0.54 for metoprolol and isoniazid, respectively). Conclusion : The effect of age on the metabolic activities of CYP2D6 and N-acetyltransferase was not significant. Therefore, dosage adjustment according to age may not be necessary for the drugs that are eliminated through these enzymes and a confirmatory study is need.