• 응용통계연구
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• 제33권2호
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• pp.203-213
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• 2020

자기-대조 환자군(self-controlled case series; SCCS) 연구는 별도의 대조군 없이 환자의 비노출기간을 대조기간으로 설정하여 노출기간에 대한 상대적인 발생 위험도를 측정하는 역학 연구의 한 방법이다. 이 방법은 대조군을 선정할 때 발생하는 편의를 최소화할 수 있는 장점이 있어서 약물 복용 후 이상반응 발생 위험도를 측정하기 위한 방법으로 전통적으로 많이 사용되어왔다. 본 연구는 SCCS 연구를 바탕으로 두 개 이상의 약물을 동시에 사용했을 때 그 부작용의 위험이 어떻게 증가하는지 살펴보고자 한다. 마약성 진통제 유사체인 tramadol과 다빈도 병용 약물 간 약물상호작용에 대해 조건부 포아송 모형을 가정하고 분석하였다. 이때 베이지안 추론법을 사용하여 최대가능도추정량이 지니고 있는 과대적합 문제를 해결하며, 사전분포의 민감도를 측정하기 위해 정규 사전분포와 라플라스 사전분포를 가정하여 모형화하였다.

• 대한한방내과학회지
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• 제30권1호
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• pp.181-190
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• 2009

It is important to establish the safety of herbal medicine because of its frequent and widespread use in Korea. Several studies on the safety of herbal medicine have been performed and there have been rare serious adverse drug reactions from those reports in Korea. However, the results are not strongly supported because of not adopting appropriate enough research methodology as to make the safety issue clear. For improving the quality of the safety research on herbal medicine. including investigations of drug induced liver injury (DILl). the aim of this study was to suggest herbal medicine-induced liver injury investigation forms for performing reasonable safety research. After a systematic review of the preceding studies regarding herbal safety in Korea was performed in 2008, we assessed the quality and the limitations of the primary studies. Two investigation forms for herbal safety research were made as a following step. one a basic investigation form for herbal safety research and the other an advanced investigation form for suspected DILl cases, Those forms include the essential informations and data needed to make an appropriate assessment of whether DILl occurred during or after the use of herbal medicine. Guidelines for using those forms and other recommendations were also suggested. More rigorous studies are required for answering the safety issue of herbal medicine as well as the efficacy issue. We hope for wide use and improvement of those investigation forms in the study of herbal safety by many researchers for establishing better evidences in Korea.

• 한국컴퓨터정보학회논문지
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• 제26권11호
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• pp.217-225
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• 2021

이 논문은 데이터 큐잉 알고리즘과 의약품 빅데이터를 통해 약품 성분-성분 간의 정보와 질병-성분 간의 정보를 지원함으로써 의약품 다약제 복용 시 부작용이 발생 가능한 약물 정보를 사용자에게 제공하기 위한 시스템을 제안하고 구현한다. 또한, 의약품 성분에 더하여 복용이 금지된 의약품, 공급업체, 유통업체의 정보 등을 제공함으로써 의료 전문가뿐만 아니라 일반 사용자의 의약품 복용에 대한 불안감을 덜어줄 수 있다. 제공되는 대표적인 정보는 두 가지 약물 사이에서 일어나는 부작용, 특정 의약품의 주성분과 효능, 동일한 제약회사에서 제조된 의약품, 만성 질환 환자가 주의해야 할 약품 성분 정보이다. 앞으로, 희귀병 약이나 신약에 대한 정보를 수집하여 데이터를 업데이트하는 것이 필요하다.

• Genomics & Informatics
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• 제16권3호
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• pp.52-58
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• 2018

In this report, we present a case study of how pharmacogenomics and pharmacometabolomics can be useful to characterize safety and pharmacokinetic profiles in early phase new drug development clinical trials. During conducting a first-in-human trial for a new molecular entity, we were able to determine the mechanism of dichotomized variability in plasma drug concentrations, which appeared closely related to adverse drug reactions (ADRs) through integrated omics analysis. The pharmacogenomics screening was performed from whole blood samples using the Affymetrix DMET (Drug-Metabolizing Enzymes and Transporters) Plus microarray, and confirmation of genetic variants was performed using real-time polymerase chain reaction. Metabolomics profiling was performed from plasma samples using liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. A GSTM1 null polymorphism was identified in pharmacogenomics test and the drug concentrations was higher in GSTM1 null subjects than GSTM1 functional subjects. The apparent drug clearance was 13-fold lower in GSTM1 null subjects than GSTM1 functional subjects (p < 0.001). By metabolomics analysis, we identified that the study drug was metabolized by cysteinylglycine conjugation in GSTM functional subjects but those not in GSTM1 null subjects. The incidence rate and the severity of ADRs were higher in the GSTM1 null subjects than the GSTM1 functional subjects. Through the integrated omics analysis, we could understand the mechanism of inter-individual variability in drug exposure and in adverse response. In conclusion, integrated multi-omics analysis can be useful for elucidating the various characteristics of new drug candidates in early phase clinical trials.

• 대한약침학회지
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• 제24권3호
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• pp.107-121
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• 2021

Objectives: The purpose of this study is to analyze the efficacy of traditional Chinese medicine (TCM) injections specified in the clinical guideline for COVID-19 by conducting a meta-analysis of viral pneumonia data. Methods: TCM injections data on viral pneumonia were collected until July 31, 2021. CNKI, PubMed, EMBASE, and the Cochrane electronic database were used to collect the clinical data. "COVID-19," "Viral pneumonia," "Tanreqing," "Xiyanping," "Reduning," "Xingnaojing," "Xuebijing," "Shenmai," "Shengmai," and "Shenfu" were used as keywords. All data collected were mainly about TCM injections and viral pneumonia. Furthermore, studies that included results such as the total effective rate, cough disappearance time, antipyretic time, lung rhomboid disappearance time, and adverse drug reaction were collected for the meta-analysis to identify the efficacy of TCM injections. However, data unrelated to TCM injections specified in the clinical guidelines for COVID-19 or viral pneumonia were excluded. The quality of included RCTs was assessed by the Cochrane Risk of Bias Tool, and Review Manager 5.3 software was used to conduct the meta-analysis. Results: A total of 18 studies with 1540 patients were included in this study. The results of the meta-analysis showed that the total effective rate OR = 4.61 (95% CI 2.92, 7.25, p = 1.00/ I² = 0%); the cough disappearance time: SMD -1.23 (-1.37, -1.09, p < 0.00001/ I² = 94%); the antipyretic time: SMD -1.26 (-1.40, -1.11, p < 0.00001/ I²=94%); lung rhomboid disappearance time: SMD -1.17 (-1.33, -1.02, p < 0.00001/ I² = 89%); and adverse drug reaction was OR 0.36 (95% CI 0.20, 0.64, p = 0.21/ I² = 30%). From the results, the treatment group (TCM injection) showed better efficacy than the control group (Western medication). Conclusion: Xiyanping, Reduning, and Tanreqing injections may yield benefits as COVID-19 treatments. However, clinical trials on TCM injections for the treatment of COVID-19 are still lacking. More high-quality clinical trials are still required.

• Journal of Ginseng Research
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• 제42권4호
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• pp.571-576
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• 2018

Background: Korean Red Ginseng (KRG) has been used in Asia for its various biological effects, but no studies have investigated the safety of its long-term intake. Therefore, the present study evaluated the safety of KRG intake for 24 weeks. Methods: We randomized 1,000 participants in a 1:1 ratio into two groups, which were treated daily with 2 g of KRG or a placebo for 24 weeks. The primary endpoint was all adverse events and adverse drug reactions (ADRs) that occurred after KRG or placebo administration, which were reported at week 4, 12, and 24 after the baseline visit. Results: In total, 192 and 211 participants experienced adverse events in the KRG and placebo groups (39.2% and 42.0%, respectively; p = 0.361), and 59 and 57 KRG- and placebo-treated individuals reported ADRs (12.0% and 11.4%, respectively; p = 0.737). The frequently occurring ADRs were pruritus (2.0%), headache (1.6%), diarrhea (1.4%), and dizziness (1.2%) in the KRG group and pruritus (2.0%), headache (1.8%), dizziness (1.6%), rash (1.4%), and diarrhea (1.2%) in the placebo group. Discontinuation of drug administration due to ADRs was reported in 13 participants, six (1.2%) and seven (1.4%) in the KRG and placebo groups, respectively (p = 0.814). No significant abnormal changes were revealed by anthropometric, laboratory, and vital sign measurements in the KRG group compared with those in the placebo group. Conclusion: The present study confirms the safety and tolerability of daily intake of 2 g of KRG for 24 weeks by healthy adults.

• Journal of Pharmaceutical Investigation
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• 제9권3호
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• pp.1-8
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• 1979

The main route of metabolism of isonicotinic acid hydrazid (INH) in man is its conjugation with acetyl coenzyme A to form acetyl-INH. The reaction is catalyzed by an N-acetyl transferase in the liver. The acetylated drug can be excreted by the kidney more efficiently than INH, and the biological half-life of the drug in the body depends upon how rapidly the drug can be acetylated. This report measured the concentration of INH in the blood of 147 individuals 6 hours after they received a standard dose (9.8mg/kg) and plotted the data as a frequeney distribution hiotogram. There was bimodality, with a mean for one subpopulation at approximately $0.6{\sim}0.8\;mcg/ml.$, and a mean for the other subpopulation between 2.8 and 4.0mcg/ml. As might be expected slow acetylators of INH are more likely to develop a cumulative toxicity to the drug. The principle ,toxicity to INH is a peripheral neuritis but this adverse effect can be prevented by given extra pyridoxin to the patients, and the vitamin does not alter the antitubercular activity of INH. This report carried out that pyridoxine does not alter the ratio of free INH to the total INH in blood.

• Journal of Oral Medicine and Pain
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• 제42권1호
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• pp.20-24
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• 2017

Drug-induced gingival overgrowth (DIGO) is an adverse drug reaction mainly described with three types of commonly prescribed drugs, namely, calcium channel blockers (CCBs) (nifedipine, diltiazem, and verapamil), anti-convulsants (phenytoin), and immunosuppressive agents (cyclosporine). Numerous reports have associated gingival overgrowth with the newer generation of immunosuppressive agents (tacrolimus, sirolimus, and everolimus), and CCBs (amlodipine, felodipine, nicardipine, and manidipine). Especially, patients concomitantly medicated with an immunosuppressive agent and CCB have a higher DIGO chance. Dentists need to be aware of drugs that induce gingival overgrowth, the possibility of DIGO, and risk factors, and also prevent the progression of DIGO by early detection of DIGO, consultation about the drug change, and the maintenance of strict dental hygiene regimes.

• Journal of Preventive Medicine and Public Health
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• 제35권1호
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• pp.41-48
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• 2002

Objectives : To review the drug prescription pattern of antiulcerative agents for elderly inpatients, Methods : The study population comprised inpatients of community hospitals who were members of the Korean Elderly Pharmacoepidemiologic Cohort (KEPEC), aged 65 years or over, beneficiaries of the Korea Medical Insurance Corporation (KMIC) and residing in Busan city in 1993. The drug prescription information was collected from the claims data of hospitals where the cohort members received medical care between January 1993 and December 1594. The information included personal identification, age, gender, diagnosis, drug dosage, date of hospital admission and name of medical institutions where the study subjects received drug prescriptions. The data analysis produced outcomes in terms of distribution of antiulcerative agents by class and by medical institution and trend of relative prescription, Analysis was also performed in terms of combined prescriptions of antiulceratives and drugs that could induce risk from drug interaction with antiulceratives. Results : The number of patients prescribed antiulcerative agents was 1,059 (64,9%) male and 1,724 (65.5%) female among the total inpatients. An antacid and composite agent was the most frequently prescribed antiulcerative agent (70.8%), followed by $H_2$ antagonist (16.0%), Among the potential drugs that could induce risk from drug interaction with the antiulcerative agents, diazepam was the most frequently prescribed. The proportion of diazepam co-prescription was 22.5% of the total cimetidine prescriptions and 14.5% of the fetal omeprazole prescriptions. Conclusions : Antiulcerative drugs were frequently prescribed in the elderly inpatients. The adverse drug reaction could possibly be due to drug interaction. The study results could be used as fundamental data for further drug utilization review of antiulceratiye agents.

• Journal of Korean Neurosurgical Society
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• 제56권5호
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• pp.448-450
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• 2014

Nefopam, a centrally acting analgesic, has been used to control postoperative pain. Reported adverse effects are anticholinergic, cardiovascular or neuropsychiatric. Neurologic adverse reactions to nefopam are confusion, hallucinations, delirium and convulsions. There are several reports about fatal convulsive seizures, presumably related to nefopam. A 71-year-old man was admitted for surgery for a lumbar spinal stenosis. He was administered intravenous analgesics : ketorolac, tramadol, orphenadrine citrate and nefopam HCl. His back pain was so severe that he hardly slept for several days; he even needed morphine and pethidine. At 4 days of administration of intravenous analgesics, the patient suddenly started generalized tonic-clonic seizures for 15 seconds, and subsequently, status epilepticus; these were not responsive to phenytoin and midazolam. After 3 days of barbiturate coma therapy the seizures were controlled. Convulsive seizures related to nefopam appear as focal, generalized, myoclonic types, or status epilepticus, and are not dose-related manifestations. In our case, the possibility of convulsions caused by other drugs or the misuse of drugs was considered. However, we first identified the introduced drugs and excluded the possibility of an accidental misuse of other drugs. Physicians should be aware of the possible occurrence of unpredictable and serious convulsions when using nefopam.