Search

The spatiotemporal distributions of latest frost dates (LFDs) on the Korean Peninsula and the atmospheric circulation patterns that resulted in the latest frosts (LFs) were investigated through the use of historical records and modern weather observation data. During the modern observation period since 1904, the most recent record of LF was April 28, 2013 at Daegwallyeong. On average, the LF occurred in Korea between March 17 (at Wando) and May 10 (at Daegwallyeong). Positive correlations were found between LFD and altitude and latitude. Additionally, inter- annual variation of LFD showed a trend of progressively earlier dates at 32 of the 48 stations at which data were available. The historic data set consists of the following: 39 records of frosts during the Three-States Period (57 BC-998 AD): 34 records during the Goryeo Dynasty (998-1391), among which the latest record was in July of the lunar calendar: and 498 during the Joseon Dynasty (1392-1928) with one LF dated August 31, 1417 on the solar calendar. Regarding LFD from The Annals of the Joseon Dynasty, April has 11 records, May has 55, June has 46, July has 21, and August has 5 LFD records. Various meteorological causes of the latest LF were then established. Firstly, a cold and humid north-easterly current that originates from high latitudes of more than 50°N and passes through the East Sea is considered one of the dominant causes of LF. Secondly, strong radiative cooling under clear skies is suspected as another important cause. Thirdly, a specific pressure pattern, called the 'inverted-S contour' or 'North High and South Low (NHSL) pattern' was found to be a favorable condition for LF. Finally the latest LF was not found to be related to monthly or longer-term cold climate, but are instead linked to the abrupt development of a strong ridge over inland Asia and the unusual southward movement of the tall polar cyclone over the North Pacific Ocean. [ABSTRACT FROM AUTHOR]

Objectives: To perform a comparison between health behaviors and health status of employees with those of the general population, to evaluate the association between employee health behaviors, health status, and absenteeism. Methods: Cross-sectional study enrolled 2433 employees from 16 Korean companies in 2014, and recruited 1000 general population randomly in 2012. The distribution of employee health behaviors, health status, and association with absenteeism were assessed. Results: Employees had significantly worse health status and low rates of health behaviors maintenance compared with the general population. Multiple logistic regression model revealed that regular exercise, smoking cessation, work life balance, proactive living, religious practice, and good physical health status were associated with lower absenteeism. Conclusions: Maintaining health behaviors and having good health status were associated with less absenteeism. This study suggests investment of multidimensional health approach in workplace health and wellness (WHW) programs. [ABSTRACT FROM AUTHOR]

Background A new controlled-release formulation of sarpogrelate, a 5-hydroxytryptamine receptor subtype 2 antagonist that blocks serotonin-induced platelet aggregation, has been developed for once-daily administration. Objective This study evaluated the effect of food on the pharmacokinetic properties of controlled-release sarpogrelate (sarpogrelate CR) in healthy volunteers. Methods A randomized, open-label, two-period, two-treatment crossover study was performed in healthy male Korean subjects. Following an overnight fast, a single dose of sarpogrelate CR 300 mg was administered either in the fasted condition or immediately after a high-fat breakfast. Pharmacokinetic parameters were calculated using a noncompartmental analysis. Tolerability was determined using clinical laboratory testing and physical examination, including vital sign measurements, electrocardiography, and interviews with the volunteers regarding adverse events (AEs). Results A total of 24 healthy subjects were enrolled, 23 of whom completed the study (mean [range] age, 26 years [21-45]; weight, 68.1 kg [56.0-79.9]; body mass index, 22.1 kg/m² [18.8-25.0]). Sarpogrelate Cmax and AUClast were decreased In the fed condition compared with those in the fasted condition, with geometric mean ratios (90% CI) of 0.4868 (0.4041-0.5864) and 0.7394 (0.6809-0.8028), respectively. Tmax was delayed from 0.75 to 4.0 hours after a high-fat meal, but the fed condition exhibited a similar elimination profile to that of the fasted condition. The most commonly reported AE was headache (n = 2), and other AEs were reported in 1 subject each. All of the AEs were considered mild in intensity, and the participants recovered without treatment. Conclusions Compared with the administration of sarpogrelate CR 300 mg in the fasted condition, administration with food was associated with a decreased rate and extent of absorption, as assessed by Cmax and AUClast, respectively. The drug was well-tolerated by the healthy subjects in this study. [ABSTRACT FROM AUTHOR]

Background Dual antiplatelet therapy with clopidogrel plus acetylsalicylic acid (ASA) is used for the treatment of acute coronary syndrome. A combined formulation of ASA and clopidogrel has been developed to provide dosing convenience and improve adherence. Objective This study was designed to compare the pharmacokinetic properties and safety profile of a fixed-dose combination formulation of ASA and clopidogrel with concurrent administration of each agent in healthy male Korean volunteers. Methods This single-dose, randomized, open-label, 2-period crossover study was conducted in 64 healthy Korean volunteers. Equal numbers of eligible participants were randomly assigned to receive either the fixed-dose combination of ASA 100 mg and clopidogrel 75 mg or the free combination of each agent followed by a 7-day washout period and then administration of the alternate formulation. Serial blood samples were collected immediately before and after dosing for 24 hours. The safety profile was evaluated by using adverse events (AEs), which were assessed by physical examination, vital signs, ECGs, clinical laboratory tests, and interviews. The 2 formulations were considered to be bioequivalent if the 90% CIs for the log-transformed Cmax and AUC0--last values were within the predetermined range of 0.8 to 1.25. Results Sixty-four volunteers (mean [SD] age, 27.51 [8.15] years; weight, 68.55 [7.86] kg; height, 173.80 [5.94] cm) were enrolled, and 63 completed the study. For ASA, the 90% CIs for the geometric mean ratios of Cmax and AUC0--last were 0.9483 to 1.1717 and 0.9946 to 1.1020, respectively. For salicylic acid, the 90% CIs were 0.9614 to 1.0396 for Cmax and 0.9778 to 1.0163 for AUC0--last. For clopidogrel, the 90% CIs were 0.9809 to 1.2562 for Cmax and 0.9674 to 1.2073 for AUC0--last. Six of the 20 AEs reported were drug related: decreased hemoglobin levels (n = 2), fever (n = 1), and headache (n = 1) with the test formulation and increased alanine aminotransferase levels (n = 1) and dyspepsia (n = 1) with the reference formulation. All of the drug-related AEs were transient and mild in severity. Conclusions The fixed-dose combination of ASA and clopidogrel 100 mg/75 mg did not meet the regulatory criteria for bioequivalence as defined by the Korea Food and Drug Administration. Both formulations were well tolerated in these healthy male Korean subjects. [ABSTRACT FROM AUTHOR]

Busulfan is an antineoplastic agent with a narrow therapeutic window. A post-hoc population pharmacokinetic analysis of a prospective randomized trial for comparison of four-times daily versus once-daily intravenous busulfan was carried out to search for predictive factors of intravenous busulfan (iBu) pharmacokinetics (PK). In this study the population PK of iBu was characterized to provide suitable dosing recommendations. Patients were randomized to receive iBu, either as 0.8 mg/kg every 6 h or 3.2 mg/kg daily over 4 days prior to hematopoietic stem cell transplantation. In total, 295 busulfan concentrations were analyzed with NONMEM. Actual body weight and sex were significant covariates affecting the PK of iBu. Sixty patients were included in the study (all Korean; 23 women, 37 men; mean [SD] age, 36.5 [10.9] years; weight, 66.5 [11.3] kg). Population estimates for a typical patient weighing 65 kg were: clearance (CL) 7.6 l/h and volume of distribution (Vd) 32.2 l for men and 29.1 L for women. Inter-individual random variabilities of CL and Vd were 16% and 9%. Based on a CL estimate from the final PK model, a simple dosage scheme to achieve the target AUC0-inf (defined as median AUC0-inf with a once-daily dosage) of 26.18 mg/l·hr, was proposed: 24.79·ABW0.5 mg q24h, where ABW represents the actual body weight in kilograms. The dosing scheme reduced the unexplained interindividual variabilities of CL and Vd of iBu with ABW being a significant covariate affecting clearance of iBU. We propose a new simple dosing scheme for iBu based only on ABW. [ABSTRACT FROM AUTHOR]

Abstract: Background: Pitavastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, and valsartan, an angiotensin receptor blocker, are used concurrently in some patients who are both hyperlipidemic and hypertensive. However, to date, no published studies have explored whether there is an interaction between pitavastatin and valsartan. Objective: The aim of this study was to investigate the potential pharmacokinetic interaction between pitavastatin and valsartan in healthy male volunteers in Korea. Methods: A randomized, open-label crossover study was conducted in healthy male Korean volunteers. In varying sequences, each subject received pitavastatin 2 × 2 mg, valsartan 2 × 160 mg, and both treatments, once daily for 7 consecutive days, with a 7-day washout period between each treatment period. Plasma samples were obtained at steady state for the pharmacokinetic evaluation of pitavastatin and valsartan. Pharmacodynamic assessment included lipid profiles and vital sign measurements (systolic and diastolic blood pressure [SBP and DBP, respectively] and pulse rate [PR]). A safety profile assessment, which included vital sign measurements, ECG, and clinical laboratory testing, was performed in each subject. Results: A total of 24 subjects were enrolled (mean age, 30.5 years [range, 23.0−45.0 years]; mean body weight, 71.2 kg [range, 56.1−86.0 kg]; and mean body mass index, 23.2 kg/m2 [range, 19.2−25.8 kg/m2]). The 95% CIs of the geometric mean ratios of AUCτ and Cmax,ss of pitavastatin were 0.97 to 1.11 and 0.73 to 1.09, respectively. The 95% CIs of the geometric mean ratios of AUCτ and Cmax,ss of valsartan were 0.90 to 1.27 and 0.81 to 1.29. Pitavastatin administered as monotherapy and in combination with valsartan was associated with significantly lowered total cholesterol and LDL-C compared with valsartan monotherapy (both, P < 0.05). Differences in lipid-lowering effects were not statistically significant between pitavastatin monotherapy and pitavastatin combined with valsartan. Valsartan monotherapy and valsartan combined with pitavastatin were associated with significantly lower SBP and DBP compared with baseline (both, P < 0.05), although no significant changes in PR were observed. No significant differences in BP or PR changes were noted between concurrent administration of valsartan monotherapy compared with pitavastatin + valsartan. There were no serious AEs reported, and none of the subjects discontinued the study due to AEs. Conclusions: The pharmacokinetic profiles of pitavastatin and valsartan administered as monotherapy were comparable to combination treatment in these healthy male Korean volunteers, suggesting that individual pharmacokinetic properties are not significantly affected by concurrent administration. The concurrent administration of pitavastatin and valsartan was generally well tolerated. The findings from the present study provide a basis for a larger study in hypertensive patients with hyperlipidemia. ClinicalTrials.gov identifier: NCT01232049. [Copyright &y& Elsevier]

To clarify the seed germination characteristics among cultivated Perilla crop and their weedy types in Korea, we studied the germination percent and germination energy of 162 accessions (102 cultivated var. frutescens, 41 weedy var. frutescens, and 19 weedy var. crispa) in both conditions of 4° low temperature treatment and non-cold treatment. In our study, most accessions of cultivated var. frutescens showed more than 50% in both germination percent and germination energy in both cold and non-cold treatment conditions. Whereas, most accessions of weedy var. frutescens and weedy var. crispa showed lower than 50% in both germination percent and germination energy in both cold and non-cold treatment. In addition, most accessions of Perilla crop and their weedy types showed much higher germination percent and germination energy in 4? low temperature treatment condition compared to the seeds under non-cold treatment condition. The information provided in this research may help for our understanding the variation of seed germination characteristics among accessions of cultivated Perilla crop and their weedy types in Korea. [ABSTRACT FROM AUTHOR]

Abstract: The effects of acupuncture on healing of deep second degree burns were compared to the conventional hydrocolloid dressing, Duoderm in mice. The expression level of inflammatory protein-1α (MIP-1α) was significantly reduced in the injured skin and the number of eosinophils in blood decreased significantly following the acupuncture treatment compared to the Duoderm dressing at 7 days after the burn. In addition, the acupuncture treatment was more effective in decreasing the wound size and inducing epidermal regeneration. Histological findings also revealed that there was less leukocyte infiltration and a greater reduction in the immunohistochemical reaction to MIP-2 in the wounds treated with acupuncture versus Duoderm. Furthermore, the numbers of BrdU- and basic fibroblast growth factor (bFGF)-positive cells were significantly increased by the acupuncture treatment, compared to the Duoderm treatment at 7 days. Moreover, in the acupuncture treated mice, the expression of fibronectin was increased and α-SMA was decreased at 7 days. Thus, this present study demonstrates that acupuncture accelerates the skin regeneration process following deep second degree burns. [Copyright &y& Elsevier]

Purpose: This study was done to investigate the relationship between critical thinking disposition and clinical competence among nurses in general hospitals. Methods: This study was a descriptive-correlational study with a convenience sample of 560 nurses from 5 general hospitals. The data were collected by sen-administered questionnaires. Critical thinking disposition was measured using the Critical Thinking Disposition Scale for Nursing Students. Clinical competence was measured using the Standardized Nurse Performance Appraisal Tool. Results: The mean score for critical thinking disposition and clinical competence was 3.37 and 4.10 respectively on a 5 point scale. A statistically significant correlation was found between critical thinking disposition and clinical competence. A regression model explained 72.8% of clinical competence. Prudence is the most significant predictor of clinical competence (R2=.728). Conclusion: Study findings suggest that nurses with a higher level of cntical thinking disposition would have a higher level of clinical competence. Furthermore, prudence might be the most important predictor of clinical competence. In order to strengthen clinical competence in nurses, the development and enhancement of cntical thinking should be emphasized at the college level and nurses should be encouraged to make a clinical decision with greater prudence. [ABSTRACT FROM AUTHOR]

Abstract: Background: As obesity is becoming an epidemic, diet programs, including low-calorie diets, are continuously being developed. It is generally believed that a low-calorie diet is commonly followed by a resting metabolic rate decrease and ultimate weight regain. Ephedra sinica and evodia rutaecarpa are known to have sympathomimetic and anti-obesity effects. Design and Objective: This study was a prospective; double-blinded, randomized and placebo-controlled clinical trial to evaluate the effects of ephedra sinica and evodia rutaecarpa on resting metabolic rate (RMR), body composition and short-term safety in obese Korean premenopausal women on a low-calorie diet. Methods: One hundred and twenty-five otherwise healthy obese women (body mass index ≥25 kg/m2) were recruited and randomly assigned to three groups: ephedra group (n = 41), evodia group (n = 45) and placebo group (n = 39). Subjects were administered ephedra extract in capsules (pseudo-ephedrine 31.52 mg) or evodia extract in capsules (evodiamine 6.75 mg, rutaecarpine 0.66 mg) or placebo capsules as well as participating in a low-calorie diet for 8 weeks. Resting metabolic rate and body composition were measured at baseline, 4 and 8 weeks. Basic serum tests were performed to evaluate the short-term safety and lipid-lowering effects of the herbs. Results: All three groups showed significant body mass index (BMI) decreases, probably due to the low-calorie diet. Among the groups, the most prominent BMI-reducing effect was seen in the ephedra group. In RMR, no significant change in any group or significant difference among the groups was found. No significant adverse effects were observed in serum tests or in the self-questionnaire. Conclusion: Ephedra combined with a low-calorie diet was effective in reducing BMI. RMR change was not compensated for by the herbal medicines tried. RMR change seemed to be affected by constitution and body composition rather than by medicine. Ephedra and evodia were proven to be safe for short-term use in the herbal form. [Copyright &y& Elsevier]

Background: CG100649, a novel selective cyclooxygenase-2 inhibitor that also inhibits carbonic anhydrase I/II, is expected to reduce the cardiovascular risk typical of other NSAIDs. Concurrent medications may influence the activities of the cytochrome P450 (CYP) 3A enzyme through which CG100649 is metabolized. Objectives: This study was designed to evaluate the influence of ketoconazole, a known strong inhibitor of CYP3A, on the pharmacokinetic properties of CG100649. Methods: This randomized, open-label, 2 × 2 crossover study was conducted in healthy Korean male volunteers. Each subject received the following 2 treatments in a randomly allocated sequence, separated by a washout period of 42 days: single oral dose of CG100649 6 mg, and concurrent dosing of CG100649 6 mg and ketoconazole 400 mg followed by ketoconazole 400 mg/d over 4 days. Blood samples for pharmacokinetic analysis were collected at 0 (predose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 240, 384, and 480 hours after dosing of CG100649 in each sequence. Tolerability assessments were performed throughout the study. Results: Thirty subjects participated, and 26 subjects completed the study. Seventeen adverse events (AEs) were reported in 10 subjects, and all AEs were recovered without any sequelae. No serious AEs were reported. Six subjects receiving the single dose of CG100649 had 9 AEs, and 7 subjects receiving the combination of ketoconazole and CG100649 had 8 AEs. The Cmax of CG100649 with CG100649 only and with concurrent administration of CG100649 + ketoconazole were similar (10.7 and 11.0 ng/mL, respectively). The CG100649 AUClast with concurrent ketoconazole was 1.29-fold greater than that with CG100649 only (2074.0 and 2685.8 ng · h/mL) and demonstrated a statistically significant difference (P < 0.05). However, there were no statistically significant differences in vital signs, clinical laboratory test results, ECGs, or AEs between treatments. Conclusion: Although the AUC of CG100649 increased by 29% with the concurrent medication of ketoconazole, it is considered that concurrent administration of CG100649 with ketoconazole would not change the safety profile of CG100649. ClinicalTrials.gov identifier: NCT01154764. [ABSTRACT FROM AUTHOR]

Background: Ivabradine, a selective inhibitor of the pacemaker current in the sinoatrial node, has shown pure heart rate (HR)-reducing effects with anti-ischemic efficacy as well as improvement in heart failure outcomes. Objective: The purpose of this study was to explore pharmacokinetic (PK) and pharmacodynamic (PD) characteristics and tolerability in healthy male Korean volunteers, as well as to compare them with PK/PD profiles of white subjects. Methods: This was a randomized, double-blind, placebo-controlled Phase I study conducted in healthy male subjects. For each of the 3 dosing groups, 9 subjects were randomized to receive ivabradine and 3 to receive placebo. Subjects received a single oral dose of ivabradine 2.5, 5, or 10 mg and after a 3-day washout period, repeat doses of 2.5, 5, or 10 mg BID for 4.5 days. Blood and urine samples were collected over 72 hours during each period, and levels of ivabradine and its metabolite S18982 were determined by using validated LC-MS/MS, followed by noncom-partmental PK analysis. For PD properties and toler-ability, 24-hour Holter recordings were obtained: at baseline, after a single dose, after repeated doses, and after the last dose. Serial resting 12-lead ECG assess-ments were also performed throughout the study. Results: Forty-eight subjects were enrolled, and 45 completed the study. After single doses of 2.5, 5, and 10 mg, respective mean Cmax levels of ivabradine were 9, 15, and 39 ng/mL, and mean AUCo-last values were 30, 52, and 121 ng • h/mL. At steady state, mean Cmax,ss levels were 11, 19, and 42 ng/mL, reached at a median Tmax of 0.67 hour for all 3 doses. The mean AUC0-t levels were 43, 58, and 139 ng • h/mL, respectively. The PK findings were linear with dose and time. Decreases in mean HR on both the Holter recordings and ECGs were observed in all of the ivabradine groups compared with placebo. After the repeated doses, mean decreases in HR were greater than those for the single doses for the same period. Statistically significant differences were observed between the 5- and 10-mg ivabradine groups and placebo. A total of 3 adverse events were reported in 2 subjects receiving ivabradine; both fully recovered without sequelae. Conclusions: Single and repeated administration of ivabradine were generally well tolerated in these healthy male Korean volunteers. Ivabradine induced significant reductions in HR, especially at doses of 5 and 10 mg. PK/PD characteristics were similar to those found in white subjects, suggesting that the dose concentration-response relationship of ivabra-dine is similar between Korean and white subjects. [ABSTRACT FROM AUTHOR]

Abstract: Background: Anastrozole is an aromatase inhibitor used to treat advanced breast cancer in postmenopausal women. A generic 1-mg tablet of anastrozole was recently developed. Objective: The study was designed to provide data to submit to Korean regulatory authorities to allow marketing of the test formulation. We evaluated the comparative bioavailability and tolerability of the test and reference formulations in healthy male adult volunteers. Methods: This single-dose, randomized, double-blind, 2-way crossover trial was conducted in the Clinical Trial Center at the Asan Medical Center (Seoul, Korea). A total of 24 healthy male Korean volunteers were enrolled. Subjects were randomized to receive 1 mg of the test or reference formulation, and pharmacokinetic (PK) parameters were measured. After a 3-week washout period, the other formulation was administered, and PK parameters were measured again. Cmax and AUClast were determined from blood samples obtained at 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, and 216 hours after drug administration. The formulations were considered bioequivalent if the 90% CIs of the geometric mean ratios of test-to-reference formulations for AUClast and Cmax were within the bioequivalence limits of 0.8 to 1.25. Nonlinear mixed-effect modeling and Monte Carlo simulations for both formulations were also conducted, and the results were used to characterize and compare the PK properties. Safety profile and tolerability were assessed using measurements of vital signs, clinical chemistry tests, and interviews. Results: All enrolled subjects completed the study. A total of 8 adverse events (AEs) were reported (2 on test formulation, 6 on reference formulation) in 7 of 24 participants. These AEs were headache (n = 1), hordeolum (n = 1), and abnormal laboratory test values (n = 6). Both formulations were well tolerated, and there were no serious AEs. Both formulations were best described by a 2-compartment disposition model with lag phase. The 90% CIs of the geometric mean ratios of test formulation to reference formulation were 0.96 to 1.08 for Cmax and 0.93 to 1.0 for AUClast. Conclusion: The test and reference formulations had similar PK parameters and similar plasma concentration-time profiles. The test formulation of anastrozole met the Korean regulatory criteria (AUC and Cmax) for assuming bioequivalence. ClinicalTrials.gov identifier: NCT01105299. [Copyright &y& Elsevier]

Abstract: Background: Dexibuprofen is a pure S(+)-enantiomer product of racemic ibuprofen. A new extended-release form of dexibuprofen has recently been developed. Objective: We aimed to compare pharmacokinetic characteristics of controlled-release (CR) and immediate-release (IR) formulations of dexibuprofen after single and multiple oral doses in fasting healthy male Korean volunteers. Methods: Both single- and multiple-dose studies used an open-label, randomized, 2-way, crossover design. In the single-dose study, 24 subjects were administered a 600-mg CR or 300-mg IR formulation. In the multiple-dose study, 24 subjects were administered a 600-mg CR formulation q12h or 300-mg IR formulation q6h. Pharmacokinetic parameters of dexibuprofen were determined by noncompartmental analysis. Results: All formulations used in the single- and multiple-dose studies were well tolerated, and there were no severe adverse events. In the single-dose study, the mean (SD) AUC0–t was 155.60 (40.94) μg/h/mL for the CR formulation and 161.11 (37.50) μg/h/mL for the IR formulation; the mean (SD) Cmax values were 22.71 (6.64) and 23.77 (4.91) μg/mL, respectively; and the median Tmax values were 2.01 hours and 2.00 hours, respectively. The geometric mean ratios (90% CI) of the CR to IR formulations were 0.96 (0.92–1.00) for AUC0–t and 1.00 (0.87–1.14) for Cmax. In the multiple-dose study, the mean (SD) AUC0–τ values for CR and IR were 129.70 (23.72) μg/h/mL and 150.04 (27.09) μg/h/mL, respectively; the mean (SD) Cmax,ss values were 24.51 (5.12) and 21.69 (5.21) μg/mL, respectively; and the median Tmax.ss values were 2.51 hours and 5.25 hours, respectively. The geometric mean ratios (90% CI) of the CR to IR formulations were 0.86 (0.81–0.91) for AUC0–τ and 1.13 (1.03–1.24) for Cmax. Conclusions: The pharmacokinetic parameters of single and multiple administrations of dexibuprofen did not differ for the IR and CR formulations in this small, selected group of healthy male Korean subjects. Both formulations were well tolerated. [Copyright &y& Elsevier]

Abstract: Background: Existing formulations of recombinant human erythropoietin (rhEPO) in Korea contain human serum albumin. To avoid the potential risk of infection by human serum albumin, a new albumin-free rhEPO has been developed. Objective: This study was conducted to characterize and compare the pharmacokinetic and safety profiles and the bioequivalence of a newly developed albumin-free rhEPO (Aropotin® [TS Corporation, Seoul, South Korea]) with 2 existing rhEPO formulations (Espogen® [LG Life Sciences, Seoul, South Korea]; Recormon® [Roche, Basel, Switzerland]) with albumin in healthy Korean subjects. Methods: This was an open-label, randomized-sequence, 3-treatment, 3-way crossover study in which healthy, nonobese (±20% of ideal weight), male volunteers between the ages of 19 and 50 years were assigned to 1 of 2 dose levels (50 IU/kg or 100 IU/kg) of 3 formulations. Blood was collected over 32 hours and plasma rhEPO concentrations were determined using a validated enzyme immunoassay. There was a 14-day washout between periods. The pharmacoki-netic parameters of the 3 formulations were compared using the bioequivalence criteria of the US Food and Drug Administration, which requires that the 90% CIs of the geometric mean ratios for AUC0−t, AUC0−∞, and Cmax fall within 0.80 to 1.25. Tolerability was evaluated by physical examination with measurements of vital signs, clinical laboratory tests, and electrocardiogram. Subjects were followed up for 2 weeks after the last administration of study drug. Results: Twelve Korean male volunteers were enrolled and completed the study. Six subjects (mean [SD] age, 22.0 [1.7] years; weight, 63.3 [6.2] kg; height, 172.3 [3.5] cm) received a single 50 IU/kg IV bolus dose of study drug and the remaining 6 subjects (mean [SD] age, 23.7 [1.5] years; weight, 66.3 [4.8] kg; height, 174 [4.7] cm) received 100 IU/kg. After a single 50 IU/kg dose, the geometric mean ratio (90% CI) for Aropotin/Espogen was 1.04 (0.91–1.19) IU/L/h for AUC0−t and 1.02 (0.89–1.17) IU/L for Cmax. The geometric mean ratio (90% CI) for Aropotin/Recormon was 1.01 (0.88−1.15) IU/L/h for AUC0−t and 1.01 (0.89–1.16) IU/L for Cmax. After a single 100-IU/kg dose, the geometric mean ratio (90% CI) for Aropotin/ Espogen was 0.98 (0.86–1.13) IU/L/h for AUC0−t and 0.99 (0.87–1.13) IU/L for Cmax. The geometric mean ratio (90% CI) for Aropotin/Recormon was 0.99 (0.861.14) IU/L/h for AUC0−t and 0.96 (0.84–1.10) IU/L for Cmax. The most frequent adverse events (AEs) were 3 occurrences of elevated serum creatine phosphokinase and serum lactate dehydrogenase levels in the Recormon 100-IU/kg group (n = 3), 3 events of elevated serum lactate dehydrogenase levels in the Espogen 100-IU/kg group (n = 3), and 4 events of elevated serum total bilirubin levels in the Aropotin 100-IU/kg group (n = 3). All formulations were well tolerated with no serious AEs. Conclusion: The new formulation of rhEPO met the regulatory criteria for bioequivalence in these healthy Korean adult male volunteers. All formulations were generally well tolerated. [Copyright &y& Elsevier]

Ivabradine, a selective inhibitor of the pacemaker current (If ), is used for heart failure and coronary heart disease and is mainly metabolized to S18982. The purpose of this study was to explore the pharmacokinetics (PK) of ivabradine and S18982 in healthy Korean volunteers. Subjects in a phase I study were randomized to receive 2.5, 5, or 10 mg of ivabradine administered every 12 hours for 4.5 days, and serial plasma and urine concentrations of ivabradine and S18982 were measured. The plasma PK of ivabradine was best described by a 2-compartment model with mixed 0- and first-order absorption, linked to a 2-compartment model for S18982. The introduction of interoccasional variabilities and period as covariate into absorption-related parameters improved the model fit. Urine data have been applied to estimate renal and nonrenal clearance, enabling a more detailed description of the elimination process. We developed a population PK model describing the plasma and urine PK of ivabradine and S18982 in healthy Korean adult males. This model might be useful for predicting the plasma and urine PK of ivabradine, potentially helping to identify the optimal dosing regimens in various clinical situations., (© 2015, The American College of Clinical Pharmacology.)

The near full-length genome consisting of four segments of dsRNA from a chrysovirus infecting Korean Cryphonectria nitschkei BS122 strain (CnV1-BS122) was sequenced. The open reading frames of segments 1, 2, 3, and 4 were 2,889, 2,721, 2,475, and 2,232 nucleotides (nt) in length, respectively. Sequence analysis and homology searches of the amino acid sequences deduced from the ORFs of each segment revealed that segments 1, 2, 3, and 4 encoded RNA-dependent RNA polymerase, capsid protein, a putative cysteine protease, and replication-associated protein, respectively. The entire 5' ends of segments 1, 2, and 4 were 82, 242, and 698 nt in length, respectively; the sequence of the 5' end of segment 3 was not determined because of difficulty in amplification. The entire 3' end of segment 3 was 77 nt in length. Partial amplification of the 3' ends of segments 1, 2, and 4 yielded amplimers of 7, 17, and 30 nt, respectively.

A total of 66 Shigella sonnei isolates from 1999 to 2008 in Seoul was analyzed for their antimicrobial resistance, carriage of integron, and the patterns of Pulsed-field gel electrophoresis (PFGE). A high level of antimicrobial resistance to streptomycin (100%), trimethoprim/sulfamethoxazole (95%), tetracycline (94%), nalidixic acid (65%), and ampicillin (41%) was observed among S. sonnei isolates. Fourteen profiles of antimicrobial resistance were identified with the most common resistance profile being nalidixic acid, streptomycin, tetracycline, and trimethoprim/sulfamethoxazole (35%). PCR and DNA sequencing analysis revealed the presence of class 2 integron in all isolates, and class 1 and 2 integrons in 7 isolates. The class 2 integron carried two types of gene cassettes. One cassette array was dfrI, sat2, and aadA1 (91%), and the other was dfr1 and sat1 (8%). dfrA12 and aadA2 gene cassette was found in one isolate containing class 1 integron. PFGE was carried out to examine the genetic relatedness among isolates. All isolates except for one showed similar PFGE patterns (similarity of 80.1%). These results suggest that the S. sonnei isolated during 1999-2008 in Seoul have similar lineages that have not undergone evolutionary changes with time.

Genetic diversity of the chrysovirus within the four fungal strains was analyzed by comparing the full-length sequences of cloned chrysoviral genes encoding the RNA-dependent RNA polymerase (RdRp) and capsid protein (CP). Because the morphological characteristics of four chrysovirus-infected Cryphonectria spp. strains were different, strain identification was conducted via sequence comparison of the internal transcribed spacers (ITSs) of the fungal rRNA gene. Phylogenic analysis of the ITS regions revealed that the four strains were closely clustered with the reference strain of Cryphonectria nitschkei, while they were more distantly related to other common Cryphonectria species, indicating that they were likely C. nitschkei. Sequence comparison among chrysoviruses from Korean C. nitschkei strains revealed that similarities of the RdRp and CP genes ranged from 98% to 100% and from 95% to 100%, respectively, at the protein level. Their corresponding nucleotide sequences showed 97% to 100% and 84% to 100% identities, respectively. Compared to RdRp, the CP gene had more divergence, suggesting the presence of genes possessing different evolutionary rates within the chrysovirus genome. Sequence comparisons with other known chrysoviruses showed that the four Korean chrysoviruses were clustered together at the next lineage level. Discovering why two strains (bsl31 and bsl32) containing identical ITS sequences and chrysoviruses display different phenotypes should prove interesting.

Little is known about the prevalence of atopic dermatitis and food allergy outside North America and Europe. We evaluated the prevalence of atopic dermatitis and food allergy with the comparison of prevalence between 1995 and 2000 in Korea and evaluated the correlation of prevalence between atopic dermatitis and food allergy. A cross-sectional questionnaire survey was conducted on random samples of schoolchildren 6 to 14 yr at two time points, 1995 and 2000 throughout Korea. The last twelve months prevalence of atopic dermatitis in Korean school-aged children was increased from 1995 to 2000. The twelve-month prevalence of atopic dermatitis and food allergy were higher in Seoul than in any other provincial cities in 1995, but the prevalence of both diseases in Seoul and Provincial Centers became to be similar in 2000. The rate responded to food allergy of children with atopic dermatitis (9.5%) was lower than that of the western countries (60%). And our data demonstrated paternal and maternal allergy history is very significantly correlated to developing atopic dermatitis in their offspring. The further objective evaluations are required to confirm these outcomes because the environmental and risk factors may be different among the countries according to their living cultures.