임상시험의 개요

신재국,차인준 인제대학교 백병원 2002 仁濟醫學 Vol.23 No.1

Clinical trial has been extensively applied not only in drug development but for the academic researches in biomedical field. Since this is an experimental research in human subjects, the highest level of ethical and scientific requirements should be asked to the investigators and their processing. Therefore, it is not surprising that clinical trial in drug development is strictly controlled by the ethical committee (institutional review board, IRB) and governmental regulations. Good clinical practice (GCP) has been developed as a guideline to keep the ethical and scientific requirements of clinical trial. Unreliable data obtained from non-scientific approach can not be used for the bess application of drugs or medical devices in to patients, which is not ethical in terms of their unnecessary exposure in human subjects. The most ideal type of clinical trial includes prospective, randomized, controlled and double-blinded approach. This short review introduces some of the important concepts in clinical trial, especially in the design and preparation of protocol.

약물반응의 다양성과 약물유전학 : A Principle for the Personalized Pharmacotherapy

신재국,차인준 인제대학교 백병원 2002 仁濟醫學 Vol.23 No.2

Individual variation in drug response is a major problem of clinical practice and of a drug development. These variation can range from therapeutic failure to adverse or even fatal effects of drugs in some patients. The incidence of serious and fatal adverse drug reactions (ADRs) has been reported to be 6.7% and 0.32% of hospitalized patients in USA, respectively. The risk for therapeutic failure or toxicity of a drug in an individual patient is determined by the interaction of genes and environment. Environmental factors include drug-drug interactions, patient's age, weight, renal and liver dysfunction, or other disease factors or clinical variables such as smoking and alcohol consumption. Many of these environmental factors have long been considered in determining the individualized dose regimen in conventional pharmacotherapeutics. However, inherited individual variability of drug responses has been left as a so called "idiosyncrasy" that are not predictable by physicians. Recently, the rapid development of pharmacogenetics/pharmacogenomics provide us extensive informations regarding on the genetic background on the wide inter-individual variation of drug responses, which is expected to lead to the era of personalized pharmacotherapy. Pharmacogenetics is a science that is interesting to the inherited variants of genes related to pharmacokinetics (drug metabolizing enzymes, drug transporters etc.) and pharmacodynamics (receptor, ion channel, target enzyme etc.), which are associated to the susceptibility of an individual to the higher risk of ADR or therapeutic failure. This review addresses the role of pharmacogenetics/pharmacogenomics in relation to wide interindividual variation of drug responses and to the possible contribution to the prediction of personalized pharmacotherapy.

만성 신부전 환자에서 혈액투석에 의한 Isoniazid의 제거

신재국,차인준,장인진,신상구,김윤구,한진석,김성권 大韓臨床藥理學會 1994 臨床藥理學會誌 Vol.2 No.2

Prednisolone과 Prednisone의 임상약동학적 평가

신재국,윤영란,차인준,이경훈,장인진,신상구,박찬웅 大韓臨床藥理學會 1994 臨床藥理學會誌 Vol.2 No.1

Nortriptyline 제제의 생물학적 동등성에 관한 연구

신재국,차인준,장인진,정원석,김용식,박찬웅,신상구 大韓臨床藥理學會 1993 臨床藥理學會誌 Vol.1 No.1

임상시험의 개요

신재국,차인준 인제대학교 백병원 2002 仁濟醫學 Vol.23 No.5

Clinical trial has been extensively applied not only in drug development but for the academic researches in biomedical field. Since this is an experimental research in human subjects, the highest level of ethical and scientific requirements should be asked to the investigators and their processing. Therefore, it is not surprising that clinical trial in drug development is strictly controlled by the ethical committee(institutional review board, IRB) and governmental regulations. Good clinical practice(GCP) has been developed as a guideline to keep the ethical and scientific requirements of clinica??trial. Unreliable data obtained from non-scientific approach can not be used for the best application of drugs or medical devices in to patients, which is not ethical in terms of their unnecessary exposure in human subjects. The most ideal type of clinical trial includes prospective, randomized. controlled and double-blinded approach. This short review introduces some of the important concepts in clinical trial, especially in the design and preparation of protocol.

혈액 종양환자에서 Tobramycin의 임상약동학

신재국,신완균,장인진,신상구,김성민,배현주,최강원,김진규 대한화학요법학회 1990 대한화학요법학회지 Vol.8 No.1

항암화학요법을 받고 있던 중 감염으로 tobramycin을 투여받은 36명의 혈액종양 환자에서 tobramycin의 약동학적 특성을 비종양환자군에서의 population 값과 비교 검토하였다. 이들은 모두 정상 신기능을 가진 16세 이상의 성인남녀(21:15)백혈병 환자들이었다. 36명의 혈액종양 환자에서 산출된 tobramycin의 청소율 및 체내분포용적은 각각 120.3± 27.2ml/lg/hr 및 0.386± 0.11 L/㎏로 population 추정 치보다 유의하게 큰 값을 보였다.(P. <0.05).청소율과 체내분포용적을 해당 population 추정치로 나눈 비율치(ratio)의 평균값은 각각 1.47± 0.34 및 1.20± 0.34였다. 연령, hematocrit치, 혈청albumin치, 발열 및 항암화학요법기간과 tobramycin의 청소율 및 체내분포용적 사이에 유의한 상관관계는 발견할 수 없었다. 본 연구결과 혈액종양 환자에서 tobramycin 투여시는 적정혈장농도를 유지하기 위해 일반 환자군에 비해 용량의 증가 및 투여간격의 조정이 필요하며 지속적인 혈장농도 monitoring을 통하여 용법의 재적정화가 필요할 것으로 사료된다. The pharmacokinetics of tobramycin were evaluated in 36 hematologic malignancy patients undergoing anticancer chemotherapy and compared to the expected values from the population parameters. Total body clearance(mean : 12.3±27.2㎖/㎏/hr) and volume of distribution (mean : 0.386±0.11 L/㎏) in hematologic malignancy patients with normal renal function were significantly greater than those of estimated from population parameter distribution(P<0.05). The ratios of total body clearance and volume of distribution to the population estimates were 1.44±0.37 and 1.20±.034, respectively. No relationships were found between age, hematocrit, serum albumin, fever or duration of anticancer chemotherapy and pharmacokinetic parameters. It is suggested that the increment of tobramycin dose regimen wold be considered in patients with hematologic malignancy, and dose readjustment followed by close monitoring of plasma drug concentration would be required.

Ciprofloxacin 제제의 생물학적 동등성에 관한 연구

최철희,신재국,신완균,유호진,이경훈,정원석,장인진,신상구 대한화학요법학회 1991 대한화학요법학회지 Vol.9 No.1

국내 시판중인 ciprofloxacin 제제인 Citopcin®(250㎎ tablet)의 동등성을 검토하기 위해 제조원인 Bayer사의 Citopcin®(250㎎ tablet)를 기준제제로 하여 18명의 건강한 남성 피험자를 대상으로 500㎎ 1회 교차 경구 투여후 약동학적 성상을 분석비교한 결과는 다음과 같다. 시험제제의 생체 이용율의 지표인 AUC, C_(mao), T_(max) 및 MRT들의 평균치는 백분율차이에 있어 모든 기준제제 지표의 ± 20% 이내였으며, 이들 생체 이용율 지표들은 분산분석 검정에서 차이를 인지할 수 없었다.생체 이용율 지표들의 기준제제에 대한 백분율 90% 대칭 신뢰구간 검토시 모든 경수들에서 ± 20% 이내의 조건을 만족하였으며 AUC의 경우에는 대칭형 신뢰구간으로 변환시 95% 신뢰구간에서도 동등성의 조건을 만족하였다, 이상의 시험결과로 시험제제인 Citopcin®은 기준제제인 Ciprobay®와 생물학적 동등한 제제로 판단되었다. The pharmacokinetics of ciprofloxacin was studied for the evaluation of the bioequivalence of the generic ciproflocacin products. Two single doses of 500㎎ each of ciprofloxacin(Ciprobay® 250㎎ tablet as a reference compound and Citopcin® 250㎎ tablet s a test compound) were administered orally to ighteen male volunteers in a balanced, randomized crossover design. Pek plasma levels of ciprofloxacin were observed about 1 hour after the doses and the peak concentrations of both products were similar(Ciprobay®, 3.18㎍/㎖; Citopcin®, 2.89㎍/㎖). The values of other pharmacokinetic parameter of ciprofloxacin computed for Ciprobay® are presented in that order: AUC=13.53:12.47㎍·h/㎖, T_(max)=1.28:1.14 hours; MRT=5.30:5.08 hours; t_(1/2)β=3.65:3.47 hours. No satistically significant, differences were detected when AUC and the other parameters were compared with the method of ANOVA. Using the criteria of 90% confidence interval for the assessment of bioequivalence al the parameters were acceptable. The products were found to be equivalent on the premise that no significant difference was detected when the relevant pharmacokinetic parameters were compared, and the confidence limit analysis showed acceptable results.

적정약물요법을 위한 약동학/약력학적 개념

손지홍,신재국 大韓臨床藥理學會 2000 臨床藥理學會誌 Vol.8 No.1

Pharmacogenomics of drug disposition: integrated understanding of gene-environmental interaction

( Jae Gook Shin ) 한국응용약물학회 2005 학술대회 Vol.2005 No.2