Evaluation of Vancomycin TDM Strategies: Prediction and Prevention of Kidney Injuries Based on Vancomycin TDM Results

The current guidelines for therapeutic drug monitoring (TDM) of vancomycin suggest a target 24-hour area under the curve (AUC 0-24 ) of 400 to 600 mg*h/L for serious methicillinresistant Staphylococcus aureus infections. In this study, the predictabilities of acute kidney injury (AKI) of various TDM target parameters, target levels, and sampling methods were evaluated in patients who underwent TDM from January 2020 to December 2020. The AUC 0-24 and trough values were calculated by both one- and two-point sampling methods, and were evaluated for the predictability of AKI. Among the AUC 0-24 cutoff comparisons, the threshold value of 500 mg*h/L in the two sampling methods was statistically significant (P = 0.042) when evaluated for the predictability of AKI. Analysis by an receiver operating characteristic curve estimated an AUC 0-24 cutoff value of 563.45 mg*h/L as a predictor of AKI, and was proposed as the upper limit of TDM target.

Comprehensive analysis of important pharmacogenes in Koreans using the DMET™ platform

Genetic polymorphisms of enzymes and transporters associated with the absorption, distribution, metabolism, and elimination (ADME) of drugs are one of the major factors that contribute to interindividual variations in drug response. In the present study, we aimed to elucidate the pharmacogenetic profiles of the Korean population using the Affymetrix Drug Metabolizing Enzyme and Transporters (DMET™) platform. A total of 1,012 whole blood samples collected from Korean subjects were genotyped using the DMET™ plus microarray. In total, 1,785 single nucleotide polymorphism (SNP) markers for 231 ADME genes were identified. The genotype and phenotype of 13 clinically important ADME genes implemented in the Clinical Pharmacogenetics Implementation Consortium guidelines were compared among different ethnic groups. Overall, the genotype frequencies of the Korean population were similar to those of the East Asian population. Several genes, notably CYP2C19 and VKORC1, showed marked differences in Koreans compared to Europeans (EURs) or Africans (AFRs). The percentage of CYP2C19 poor metabolizers was 15% in Koreans and less than 3% in EURs or AFRs. The frequencies of causative SNPs of the VKORC1 gene for the low warfarin dose phenotype were 90%, 60%, and 10% in Koreans, EURs and AFRs, respectively. Our findings can be utilized for optimal pharmacotherapy in Korean patients.

Evaluation of the pharmacokinetics and food effects of a novel formulation tamsulosin 0.4 mg capsule compared with a 0.2 mg capsule in healthy male volunteers

Tamsulosin, an alpha-1 adrenoreceptor antagonist, has been used as a primary option for medical treatment of benign prostate hyperplasia. An open-label, single-dose, randomized, three-treatment, three-period, three sequence crossover study was conducted to evaluate the pharmacokinetics (PKs) of 0.2 and 0.4 mg tamsulosin hydrochloride (HCl) in the fed versus the fasted state. Subjects were randomly assigned to three sequences and received one of the following treatments at each period: tamsulosin HCl 0.2 or 0.4 mg in the fed state with a high-fat meal, or tamsulosin HCl 0.4 mg in the fasted state. Blood samples for the PK analysis were collected at pre-dose and up to 48 h post-dose. The PK parameters were calculated by a non-compartmental method. The geometric mean ratio (GMR) and its 90% confidence intervals (CIs) of the plasma maximum concentration (C max ) and area under concentration curve from time zero to last measurable concentration (AUClast) were calculated. Twenty-two subjects completed the study. The systemic exposure of tamsulosin 0.4 mg decreased approximately 9% in the fed state compared to the fasted state, and the time to reach peak concentration was slightly delayed in the fed state. The dose normalized GMR and its 90% CIs of C max and AUClast for 0.2 and 0.4 mg tamsulosin in the fed state were within 0.8 and 1.25 range. Systemic exposure of tamsulosin was decreased in the fed condition compared to the fasted condition. Linear PK profiles were observed between 0.2 and 0.4 mg tamsulosin in the fed state.

Evaluation of the pharmacokinetics and food effects of a novel formulation tamsulosin 0.4 mg capsule compared with a 0.2 mg capsule in healthy male volunteers

Tamsulosin, an alpha-1 adrenoreceptor antagonist, has been used as a primary option for medical treatment of benign prostate hyperplasia. An open-label, single-dose, randomized, three-treatment, three-period, three sequence crossover study was conducted to evaluate the pharmacokinetics (PKs) of 0.2 and 0.4 mg tamsulosin hydrochloride (HCl) in the fed versus the fasted state. Subjects were randomly assigned to three sequences and received one of the following treatments at each period: tamsulosin HCl 0.2 or 0.4 mg in the fed state with a high-fat meal, or tamsulosin HCl 0.4 mg in the fasted state. Blood samples for the PK analysis were collected at pre-dose and up to 48 h post-dose. The PK parameters were calculated by a non-compartmental method. The geometric mean ratio (GMR) and its 90% confidence intervals (CIs) of the plasma maximum concentration (C max ) and area under concentration curve from time zero to last measurable concentration (AUClast) were calculated. Twenty-two subjects completed the study. The systemic exposure of tamsulosin 0.4 mg decreased approximately 9% in the fed state compared to the fasted state, and the time to reach peak concentration was slightly delayed in the fed state. The dose normalized GMR and its 90% CIs of C max and AUClast for 0.2 and 0.4 mg tamsulosin in the fed state were within 0.8 and 1.25 range. Systemic exposure of tamsulosin was decreased in the fed condition compared to the fasted condition. Linear PK profiles were observed between 0.2 and 0.4 mg tamsulosin in the fed state.

Subungual Juvenile Xanthogranuloma / 대한피부과학회지

Juvenile xanthogranuloma is a benign cutaneous histiocytic proliferative disorder. It usually develops on the head and the trunk, but rarely develops in the digits. To date, only two cases of subungual juvenile xanthogranuloma have been reported in the literature. We present 2 young patients who had subungual juvenile xanthogranuloma.

Community-Oriented Primary Care: Preparing Physicians for the Future in the United States / 한국의학교육

As the health care system continues to evolve, there will be a shift in the care that physicians are asked to provide: from high-tech to patient-centered, from treatment-focused to prevention-focused. To improve the health of communities, health providers need to apply skills beyond those contained in the traditional biomedical model and must strive to encompass the community-based public health model. Physicians must function effectively within a multidisciplinary team in order to provide optimal health care in a setting of complex needs which far exceed the capacity of any one health discipline to address adequately. Students need first hand experience working with population issues in all learning settings - the hospital, the clinic and the community - to stimulate their interest in a population perspective. The medical education community needs to search for innovative, creative approaches to help the students develop the knowledge skills, and attitudes to practice. Community-oriented primary care (COPC) addresses the need to train practitioners in primary care practice that is community-responsive and that includes a public health perspective. It helps bridge the gap between academic medicine and the community it is designed to serve while fostering linkages among providers and community groups. It provides the structure for the various members of a public health team, often isolated from one another within their own institutions, to share ideas that focus on the need for integrity and simplicity in a community- responsive health care system. But perhaps most importantly, it restores the social contract between medicine and society.