Evaluation of factors associated with drug-induced liver injury using electronic medical records

The causes and attributing factors of drug-induced liver injury (DILI) remain unclear as a result of exclusion-based diagnosis and low incidence. The aim of this study was to explore and evaluate potential drug-related causes and factors associated with DILI. Using electronic medical records (EMR) from the Seoul National University Bundang Hospital from 2003 to 2014, patients with DILI events were identified based on liver function test results. All patients with hepatic or biliary diseases were excluded. Patient characteristics, including demographics, clinical patterns, and severity of DILI were summarized and their associations were evaluated. Drugs frequently prescribed to patients exhibiting DILI within the month before their first DILI event compared to the total patient population were identified and the probabilities of hepatotoxicity associated with their use were assessed through examination of available reports. Among the 1,835 patients with laboratory test results, 1,023 were male and 1,053 were 65 years of age or older. Moderate DILI was dominant in older or male patients and cholestatic DILI tended to be more frequently identified in older patients of either sex. Cytarabine was the most frequently prescribed drug in DILI patients, followed by aprotinin and dopamine. Among the 30 most frequently prescribed drugs in DILI patients, 15 (50%) were identified as known hepatotoxic agents. In conclusion, this study evaluated differences in features of DILI among groups based on demographics and explored candidate drugs with possible associations with DILI, which has potential value reflecting real-world clinical practice.

A Detailed Analysis of Alcohol Pharmacokinetics in Healthy Korean Men / 대한법의학회지

To determine blood alcohol concentration (BAC) by extrapolation, an understanding of basal pharmacokinetics is indispensable. Breath alcohol concentration (BrAC) has been used for the determination of body alcohol concentration replaced by BAC in Korea. Therefore, the determination of BAC/BrAC ratio is a key problem in alcohol pharmacokinetics. Among several factors, the ingested dose of alcohol and the allelic variation of mitochondrial aldehyde dehydrogenase 2 (ALDH2) are the most significant factors influencing the pharmacokinetic parameters, particularly in the absorption and elimination phases. This study shows a detailed pharmacokinetic analysis of BAC and BrAC associated with genetic polymorphism including ALDH2 in 42 healthy Korean men. The change in the alcohol dose ingested influenced the maximum concentration (C(max)), the time to reach C(max) (T(max)), the absorption rate constant (K(01)), the area under the concentration-time curve (AUC(last)), and the hourly elimination rate. The conversion of wild-type 487Glu (ALDH2*1) to 487Lys (ALDH2*2) in human ALDH2 resulted in changes in C(max) (ALDH2*1/*1, 0.03+/-0.01 g/dL [+/-standard deviation] vs. ALDH2*1/*2, 0.05+/-0.004 g/dL [P<0.01]), AUC(last) (ALDH2*1/*1, 4.48+/-2.19 g.min/dL vs. ALDH2*1/*2, 7.52+/-1.26 g.min/dL [P<0.05]), and the BAC elimination rate (ALDH2*1/*1, 0.05+/-0.02 g/L/hr vs. ALDH2*1/*2, 0.09+/-0.01 g/L/hr [P<0.05]). Moreover, the comparison of BAC and BrAC by Bland-Altman plot showed good agreement, suggesting that the measurement of BrAC can be a good alternative for the determination of BAC, particularly in the post-absorption phase. These results provide fundamental information about the pharmacokinetics of alcohol and the determination of BAC in forensics.