약물경제학은 보건의료 경제학의 한 분야로, 특정 의약품과 비교대상 의약품의 가치 (value)를 비교하는 학문 분야이다. 약물경제학 연구는 화폐 단위로 표현되는 비용 (cost)과 의약품의 효능(efficacy), 삶의 질 향상 (quality of life, QOL), 화폐단위 가치 (value)를 평가하는 것이다. 즉, 보건의료 부문의 각종 사업, 의약품 등 건강과 관련된 사항의 비용과 성과를 경제적 도구를 사용하여 측정하고 비교하는 개념이다. 약물 경제학의 분석법은 측정하는 비용과 결과(편익)의 종류와 그 측정방법에 따라서 비용최소화 분석 (Cost-Minimization Analysis), 비용효과 분석 (Cost-Effectiveness Analysis ; CEA), 비용효용 분석 (Cost-Utility Analysis ; CUA), 비용편익 분석 (Cost-Benefit Analysis ; CBA)등이 있다. 약물경제학 연구를 통해 희소한 보건의료자원을 공정하고 효율적으로 배분하는 데 도움을 줄 수 있다. 따라서, 약물경제학 연구는 의사결정의 판단수준을 향상시키고 일관성을 제공할 수는 있다.

As the number of clinical trials in Korea has been increasing in recent years, the public start having concerns about the protection of human subjects in research. The ethical aspect of clinical trials is considered as one of the most important issues, and informed consent lies in the core of the ethical conduct of clinical research. Informed consent requires three key components to be ethically valid:information, comprehension and voluntariness. Furthermore, the consent process should be properly executed to ensure that the circumstances in which consent is obtained are free of coercion and undue influence. There are lots of challenges to conducting proper informed consent. The purpose of this article was to describe those challenges and to provide suggestions for improving informed consent.

Background: Vancomycin is an effective glycopeptide antibiotic against gram-positive infections. Vancomycin has a relatively narrow therapeutic window (5~15 mg/L) and has potentially severe adverse effects such as nephrotoxicity. In order to maintain effective drug concentrations and reduce the possibility of toxicity, therapeutic drug monitoring is useful. The pharmacokinetics of vancomycin is known to differ between pediatric and adult patients because of difference in body size, renal function, etc. This study aimed to describe the population pharmacokinetics of vancomycin in Korean pediatric patients and to evaluate the predictive performance of the population pharmacokinetic model. Methods: Vancomycin dosage histories, sampling times, concentrations and demographic data were collected retrospectively from therapeutic drug monitoring reports. Patients were randomly allocated to either the index data set (n=92) or a validation data set (n=25). The index data set was comprised of 159 concentration measurements. The population pharmacokinetic parameters of vancomycin were estimated by nonlinear mixed-effect modeling using first-order conditional estimation with interaction method. The influence of covariates such as age, weight, height, gender, serum creatinine, creatinine clearance and concomitant medicine (aminoglycosides) were assessed. The predictive performance of the models was evaluated using the validation data set. Bias and precision were assessed by mean prediction error and root mean squared error. Results: The two compartment model was adopted and the final population pharmacokinetic model related clearance to weight and serum creatinine, and central volume of distribution to weight. The final population pharmacokinetic parameters were modeled as follows: clearance (L/h) = $0.0722\;{\times}\;weigth^{1.3}\;(kg)\;{\times}$ (1 - serum creatinine (mg/dL) ${\times}\;0.506$), central volume of distribution (L) = $0.0709\;{\times}\;weight^{1.61}\;(kg)$, $k_{12}\;(1/h)\;=\;0.288$, $k_{21}\;(1/h)\;=\;0.14$. The coefficient of variations (CVs) of interindividual variability in clearance and central volume of distribution were 25.5% and 18.6%, respectively. The residual variability was 23.5%. Predictive performance of this model was evaluated using the validation data set. The mean prediction error and root mean squared prediction error were -0.17 and 2.10 mg/L, respectively. Conclusions: A population pharmacokinetic models of vancomycin in Korean pediatric patients was newly developed. Weight and serum creatinine were significant factors affecting vancomycin disposition. The predictive performance of this model was reasonably acceptable. The population pharmacokinetic parameter values of Korean pediatric patients obtained from this model may be used to optimize vancomycin therapy.

Background: Amlodipine, a dihydropyridine calcium channel blocker, is prescribed for the management of angina and hypertension. It is used therapeutically as a racemic mixture, composed of S- and R-enantiomers. However, its calcium channel blocking activity is confined to S-amlodipine; R-amlodipine has 1000-fold less activity than the S-enantiomer. Objective: The objective of this study was to compare the pharmacokinetic characteristics and safety profiles of the newly developed S-amlodipine formulation, composed of different additives, with those of the previously developed formulation. Methods: This randomized, double blind, two periods, two sequence crossover study was conducted in 24 healthy male volunteers at Seoul National University Hospital Clinical Trials Center. All subjects were randomly assigned to one of two sequence groups: (1) a single dose of the new S-amlodipine formulation (5 mg, 2.5mg/tablet) in the first study period, followed by a single dose of the reference S-amlodipine formulation (5 mg, 2.5mg/tablet) in the second study period, or (2) vice versa. A 14 day-washout separated the study periods. Blood samples for pharmacokinetic analysis of S-amlodipine were collected just before study drug administration and at predefined time points up to 168 hours post dose. Safety profiles including hematology, biochemistry, electrocardiography, and urinalysis were assessed throughout the study. Pharmacokinetics of the two formulations were characterized using noncompartmental model and compared between the formulations. Results: The pharmacokinetic profiles of S-amlodipine were comparable between the formulations. The mean [SD] values for $C_{max}$ in reference and test formulation (3.4 [0.8] ug/L vs 3.3 [0.88] ug/L, respectively) and AUC from time 0 to the last available measurement ($AUC_{last}$) (159.2 [45.6] ug*h/L vs 160.6 [48.9] ug*h/L, respectively) were similar. The calculated 90% confidence interval of the corresponding ratios of log-transformed $C_{max}$ and $AUC_{last}$, were 0.90~1.03 and 0.93~1.08, respectively. Neither formulation caused any serious adverse events. Conclusions: Both formulations were safe and well tolerated in tested dose, 5 mg of S-amlodipine. This study provides evidence for similar pharmacokinetic characteristics of the newly developed formulation of S-amlodipine to a previously prescribed formulation in healthy Korean male volunteers.

Background: Udenafil is a new phosphodiesterase (PDE) 5 inhibitor for the treatment of erectile dysfunction. The safety and efficacy of udenafil were shown in clinical studies, and two dosing regimens (100 mg and 200 mg) received marketing approval for 100 mg tablets. In this study, we compared the pharmacokinetics between udenafil 100 mg tablets and 200 mg tablets. Methods: The pharmacokinetic characteristics of the 200 mg strength formulation were compared with the 100 mg strength formulation in an open-labeled, randomized, two-way crossover study in 20 healthy male volunteers. A group of 9 subjects were dosed one udenafil 200 mg tablet and administered two 100 mg tablets one week later. Another group of 11 subjects were dosed in the opposite sequence. As an outcome, plasma udenafil concentration-time profiles were obtained. Pharmacokinetic characteristics were analyzed using the 90% confidence intervals of the geometric mean ratios for maximum plasma concentration ($C_{max}$) and the area under the concentration-time curve from time zero to infinity ($AUC_{inf}$). Results: The two dosage formulations showed similar concentration-time profiles. The geometric mean ratio of $C_{max}$ of udenafil 200 mg formulation to 100 mg formulation was 0.94 and the 90% confidence interval was 0.86-1.02. The geometric mean ratio of $AUC_{inf}$ was 0.93 and the 90% confidence interval for the two regimens was 0.87 - 1.00. Conclusion: The 200 mg tablets showed similar pharmacokinetic characteristics compared to the 100 mg tablets as judged from the 90% confidence intervals of the geometric mean ratio for $C_{max}$ and $AUC_{inf}$ that were both within a range of log 0.80 - log 1.25.