강한 한국 성인에서 ALDH2 유전형에 따라 Metadoxine(Alcotel ？？ )이 알코올의 약동학 및 약역학에 미치는 영향

The Effects of Metadoxine(Alcotel ？？ ) on Alcohol Pharmacokine and Pharmacodynamics in Normal Korean Adults with Different ALDH2 Geno

Objectives：Metadoxine is known to have accelerated the metabolism of alcohol in previous studies with Caucasian subjects. The purpose of this study was to evaluate the effects of metadoxine on alcohol pharmacokinetics and pharmacodynamics in normal Korean adults according to the low-Km aldehyde dehydrogenase (ALDH2) genotypes. Methods：Twenty healthy male volunteers (half with active ALDH2*1/*1：active group, the other with inactive ALDH2*1/*2：inactive group) were selected by genotyping. In a double-blind, counterbalanced design, each subject ingested 0.5 g of alcohol per kg of body weight with pretreatment of metadoxine or placebo on 2 separate occasions. Blood alcohol concentration by breathanalyzer (BrAC), vital signs, negative physiological responses and performance function using a battery of tests (critical flicker fusion threshold：CFFT, choice reaction time：CRT, compensatory tracking task：CTT and digit-symbol substitution：DSS) were measured at baseline and repeatedly over a 3-hour period after intake of alcohol. Results：Among the pharmacokinetic parameters, Vmax and Km were significantly increased with pretreatment of metadoxine in both the active and inactive ALDH2 groups, but the ratio of Vmax/Km was decreased. In terms of pharmacodynamics, the pretreatment of metadoxine produced a significant improvement of performance such as CFFT and DSS in the active ALDH2 group, but did not in the inactive ALDH2 group. Conclusions：It may be concluded that metadoxine has little effect on alcohol metabolism in both groups with respect to pharmacokinetics on the basis of BrAC. The pharmacodynamic results, however, indicated that metadoxine might be partially effective in counteracting the impairing effects of alcohol on the performance in the active ALDH2 group.