ABSTRACT
YH4808 is a novel potassium-competitive acid blocker developed for gastric acid-related disorders. Previous studies indicate its potential to improve symptoms of gastric acid-related disorders. The current study was aimed to find the optimal regimen of YH4808 for night time pH control. This study was performed in two parts. Each was a randomized, open-label, active-controlled, multiple-doses, two-treatment, two-period crossover study conducted in 20 healthy Korean volunteers. Subjects were randomly assigned to one of the four groups.The three groups received different dosage regimens of YH4808 (100 mg twice a day, 200 mg once a day, or 200 mg twice a day), and the fourth group received esomeprazole 40 mg twice a day. The pharmacokinetic parameters demonstrated that the systemic exposure of YH4808 increased in a dose-proportional manner. The difference in the proportion of time above pH 4 over 24 h from the baseline was the greatest in the group receiving YH4808 200 mg twice a day. The values of the area under the effect curve at night time (12 A.M.–7 A.M.) were higher in all YH4808 groups than in the esomeprazole group. However, the differences among the YH4808 groups were not statistically significant (p > 0.05). YH4808 exhibited potential for better pH control during the night in comparison to esomeprazole. The optimal regimen for night time pH control among all the YH4808 regimens was 200 mg twice a day.
ABSTRACT
Purpose@#We aimed to investigate the association between daily sunlight exposure duration and fractures in older Korean adults with osteoporosis. @*Materials and Methods@#We utilized data from the 2008–2011 Korea National Health and Nutrition Examination Survey. Osteoporosis was diagnosed based on a T-score of ≤-2.5 using dual energy X-ray absorptiometry. The duration of daily sunlight exposure and fracture were assessed via intensive health interviews by trained staff using standardized health questionnaires. Fracture was defined as one or more fractures of the femur, wrist, and spine. @*Results@#A total of 638 patients with osteoporosis aged ≥65 years were included. The odds ratio (OR) of total fractures was 0.55 times lower in the group with ≥5 h of daily sunlight exposure than in the group with <5 h of exposure after adjusting for age, sex, family history of osteoporosis or fracture, body mass index, bone mineral density of the femoral neck, serum 25-hydroxyvitamin D, current smoking, alcohol intake, daily calcium intake, and physical activity [95% confidence interval (CI) 0.31–0.97, p=0.040].In patients with vitamin D insufficiency, the OR of total fracture was 0.52 times lower in the group with ≥5 h of daily sunlight exposure than in the group with less exposure after adjusting the above variables (95% CI 0.28–0.97, p=0.041). @*Conclusion@#Sunlight exposure for ≥5 h a day was significantly associated with a decreased OR of fracture in older Korean adults with osteoporosis. This association was also significant in patients with vitamin D insufficiency.
ABSTRACT
Purpose@#We aimed to investigate the association between daily sunlight exposure duration and fractures in older Korean adults with osteoporosis. @*Materials and Methods@#We utilized data from the 2008–2011 Korea National Health and Nutrition Examination Survey. Osteoporosis was diagnosed based on a T-score of ≤-2.5 using dual energy X-ray absorptiometry. The duration of daily sunlight exposure and fracture were assessed via intensive health interviews by trained staff using standardized health questionnaires. Fracture was defined as one or more fractures of the femur, wrist, and spine. @*Results@#A total of 638 patients with osteoporosis aged ≥65 years were included. The odds ratio (OR) of total fractures was 0.55 times lower in the group with ≥5 h of daily sunlight exposure than in the group with <5 h of exposure after adjusting for age, sex, family history of osteoporosis or fracture, body mass index, bone mineral density of the femoral neck, serum 25-hydroxyvitamin D, current smoking, alcohol intake, daily calcium intake, and physical activity [95% confidence interval (CI) 0.31–0.97, p=0.040].In patients with vitamin D insufficiency, the OR of total fracture was 0.52 times lower in the group with ≥5 h of daily sunlight exposure than in the group with less exposure after adjusting the above variables (95% CI 0.28–0.97, p=0.041). @*Conclusion@#Sunlight exposure for ≥5 h a day was significantly associated with a decreased OR of fracture in older Korean adults with osteoporosis. This association was also significant in patients with vitamin D insufficiency.
ABSTRACT
YH4808 is a novel potassium-competitive acid blocker that was developed as a therapeutic agent for gastric acid-related diseases; it may replace proton pump inhibitors, which are widely used in combination with amoxicillin and clarithromycin for Helicobacter pylori eradication. We compared the pharmacokinetic (PK) profiles and safety of amoxicillin, clarithromycin, and YH4808 used as monotherapies or in combination for evaluating potential drug interactions. An open-label, randomized, single-dose, Latin-square (4 × 4) crossover study was conducted in 32 healthy Korean volunteers. Subjects were randomly assigned to one of the 4 treatment sequences that consisted of 4 periods separated by 21-day washout intervals. PK parameters of YH4808, amoxicillin and clarithromycin administered in combination were compared with those of the respective monotherapies. The geometric mean ratios of the maximum concentration (Cmax) and the area under the time-concentration curve from time zero to time of the last quantifiable concentration (AUClast) of YH4808 increased during the triple therapy by 48.6% and 29.1%, respectively. Similarly, the Cmax and AUClast of M3 (active metabolite of YH4808) increased by 23.3% and 16.0%, respectively. The Cmax and AUClast of clarithromycin increased by 27.4% and 30.5%, and those of 14-hydroxyclarithromycin were increased by 23.1% and 32.4%, respectively. The corresponding amoxicillin values decreased during the triple therapy by 21.5% and 15.6%, respectively. There was no clinically significant change in safety assessment related to either monotherapies or triple therapy. In conclusion, amoxicillin, clarithromycin and YH4808 administered as triple therapy did not exhibit significant PK interactions and were not associated with safety issues.
ABSTRACT
YH4808 is a novel selective potassium-competitive acid blocker demonstrated to be safe and to have inhibitory effects against gastric acid secretion in previous studies. A randomized, open-label, multiple-dose, 3-treatment, 1-period, parallel design study was conducted to compare the Helicobacter pylori eradication rates and acid suppression capacities of three regimens in 60 healthy subjects with H. pylori-positive, and the potential of YH4808 to replace proton-pump inhibitors (PPIs) in standard regimens for H. pylori eradication. Group 1 received YH4808, amoxicillin, and clarithromycin as a novel triple regimen, while Group 2 received YH4808 and amoxicillin only, and Group 3 received esomeprazole, amoxicillin, and clarithromycin, as the standard triple regimen. H. pylori eradication rates were 85.0% for Group 1, 25.0% for Group 2, and 83.3% for Group 3. Relative response rate between Group 1 and 3 was 1.02 (0.50–2.07; 95% CI, χ2 test p = 0.8881). Furthermore, the novel triple regimen, YH4808, amoxicillin, and clarithromycin, stably inhibited acid secretion and maintained a gastric pH greater than 4 or 5 for 24 hours, which was comparable to the pH range in the standard triple regimen. However, the onset times of the YH4808 regimens were earlier than that for the regimens using esomeprazole. There were no differences in the incidences or severity of adverse events among the three groups. Overall, the novel triple regimen was safe and well-tolerated. YH4808 could replace PPIs in standard triple regimens used for H. pylori eradication.
ABSTRACT
YH4808 is a novel selective potassium-competitive acid blocker demonstrated to be safe and to have inhibitory effects against gastric acid secretion in previous studies. A randomized, open-label, multiple-dose, 3-treatment, 1-period, parallel design study was conducted to compare the Helicobacter pylori eradication rates and acid suppression capacities of three regimens in 60 healthy subjects with H. pylori-positive, and the potential of YH4808 to replace proton-pump inhibitors (PPIs) in standard regimens for H. pylori eradication. Group 1 received YH4808, amoxicillin, and clarithromycin as a novel triple regimen, while Group 2 received YH4808 and amoxicillin only, and Group 3 received esomeprazole, amoxicillin, and clarithromycin, as the standard triple regimen. H. pylori eradication rates were 85.0% for Group 1, 25.0% for Group 2, and 83.3% for Group 3. Relative response rate between Group 1 and 3 was 1.02 (0.50–2.07; 95% CI, χ2 test p = 0.8881). Furthermore, the novel triple regimen, YH4808, amoxicillin, and clarithromycin, stably inhibited acid secretion and maintained a gastric pH greater than 4 or 5 for 24 hours, which was comparable to the pH range in the standard triple regimen. However, the onset times of the YH4808 regimens were earlier than that for the regimens using esomeprazole. There were no differences in the incidences or severity of adverse events among the three groups. Overall, the novel triple regimen was safe and well-tolerated. YH4808 could replace PPIs in standard triple regimens used for H. pylori eradication.
ABSTRACT
Fimasartan is a nonpeptide angiotensin II receptor blocker. In a previous study that compared the pharmacokinetics (PK) of fimasartan between patients with hepatic impairment (cirrhosis) and healthy subjects, the exposure to fimasartan was found to be higher in patients, but the decrease of blood pressure (BP) was not clinically significant in those with moderate hepatic impairment. The aims of this study were to develop a population PK-pharmacodynamic (PD) model of fimasartan and to evaluate the effect of hepatic function on BP reduction by fimasartan using previously published data. A 2-compartment linear model with mixed zero-order absorption followed by first-order absorption with a lag time adequately described fimasartan PK, and the effect of fimasartan on BP changes was well explained by the inhibitory sigmoid function in the turnover PK-PD model overlaid with a model of circadian rhythm (NONMEM version 7.2). According to our PD model, the lower BP responses in hepatic impairment were the result of the increased fimasartan EC₅₀ in patients, rather than from a saturation of effect. This is congruent with the reported pathophysiological change of increased plasma ACE and renin activity in hepatic cirrhosis.
Subject(s)
Humans , Absorption , Blood Pressure , Circadian Rhythm , Colon, Sigmoid , Healthy Volunteers , Linear Models , Liver Cirrhosis , Liver , Pharmacokinetics , Plasma , Receptors, Angiotensin , ReninABSTRACT
JOINS (SKI306X) is an herbal anti-arthritic medicine that is widely used with aceclofenac for treating osteoarthritis in Korea. A fixed-dose combination (FDC) tablet containing SKI306X and aceclofenac was developed to improve patient compliance. This study aimed to compare the pharmacokinetics (PK) and safety of the FDC tablet with those of co-administered SKI306X and aceclofenac in healthy subjects. In this randomized, open-label, two-way crossover, single-dose study, the FDC tablet (SKI306X 300 mg/aceclofenac 100 mg) (test) was given or co-administration of 300 mg of SKI306X and 100 mg of aceclofenac (reference) was performed followed by a 7-day wash-out period. Blood samples were collected before and after drug administration to evaluate aceclofenac PK parameters, and safety was assessed throughout the study. A total of 54 healthy male subjects were enrolled in and completed the study. T(max) and t(1/2) of aceclofenac of the FDC tablet were similar to those of aceclofenac co-administered with SKI306X (T(max): test 2.96 h and reference 2.14 h; t(1/2): test 3.46 h and reference 4.04 h). The geometric mean ratios (90% confidence intervals) of C(max) and AUC(last) (T/R) were 0.85 (0.81 to 0.91) and 1.03 (1.01 to 1.06) respectively; these results were within the predefined range (0.8 to 1.25). There was only one drug-related adverse event (dizziness) occurred after administration of the FDC tablet; however, it was mild in severity and resolved without any complications. The FDC tablet was well tolerated and exhibited an absorption rate and extent comparable to those of SKI306X and aceclofenac administered simultaneously.
Subject(s)
Humans , Male , Absorption , Healthy Volunteers , Korea , Osteoarthritis , Patient Compliance , Pharmacokinetics , TabletsABSTRACT
Atorvastatin and ezetimibe are frequently co-administered to treat patients with dyslipidemia for the purpose of low-density lipoprotein cholesterol control. However, pharmacokinetic (PK) drug interaction between atorvastatin and ezetimibe has not been evaluated in Korean population. The aim of this study was to investigate PK drug interaction between two drugs in healthy Korean volunteers. An open-label, randomized, multiple-dose, three-treatment, three-period, Williams design crossover study was conducted in 36 healthy male subjects. During each period, the subjects received one of the following three treatments for seven days: atorvastatin 40 mg, ezetimibe 10 mg, or a combination of both. Blood samples were collected up to 96 h after dosing, and PK parameters of atorvastatin, 2-hydroxyatorvastatin, total ezetimibe (free ezetimibe + ezetimibe-glucuronide), and free ezetimibe were estimated by non-compartmental analysis in 32 subjects who completed the study. Geometric mean ratios (GMRs) with 90% confidence intervals (CIs) of the maximum plasma concentration (C(max,ss)) and the area under the curve within a dosing interval at steady state (AUC(τ,ss)) of atorvastatin when administered with and without ezetimibe were 1.1087 (0.9799–1.2544) and 1.1154 (1.0079–1.2344), respectively. The corresponding values for total ezetimibe were 1.0005 (0.9227–1.0849) and 1.0176 (0.9465–1.0941). There was no clinically significant change in safety assessment related to either atorvastatin or ezetimibe. Co-administration of atorvastatin and ezetimibe showed similar PK and safety profile compared with each drug alone. The PK interaction between two drugs was not clinically significant in healthy Korean volunteers.
Subject(s)
Humans , Male , Atorvastatin , Cholesterol , Cross-Over Studies , Drug Interactions , Dyslipidemias , Ezetimibe , Lipoproteins , Pharmacokinetics , Plasma , VolunteersABSTRACT
JOINS, an herbal anti-arthritic drug, was developed for the treatment and pain relief of knee osteoarthritis. It was approved for use in Korea by the Ministry of Food and Drug Safety in 2001. The aim of this study was to investigate the effect of JOINS on the pharmacokinetic (PK) profiles of aceclofenac in healthy adults. A PK drug-drug interaction study was conducted in 61 healthy subjects by using an open-label, multiple-dose, one sequence, two-period design. Blood samples were collected for plasma concentrations of aceclofenac during the reference period (aceclofenac 100 mg alone) and interaction period (aceclofenac 100 mg + JOINS 300 mg). The area under the curve within a dosing interval (τ) at steady state (AUC(τ,ss)) and the C(max) at steady state (C(max,ss)) of aceclofenac were analyzed by a non-compartment model using the Phoenix® WinNonlin® software version 6.3 (Pharsight, Mountain View, CA, USA). The 90% CIs of the geometric mean ratios (GMRs) of the AUC(τ,ss) of aceclofenac with JOINS to without JOINS (D4/D3 and D11/D3) were 0.9593–1.0130 and 0.9745–1.0291, respectively, and the corresponding values for the C(max,ss) of aceclofenac with JOINS to without JOINS (D4/D3 and D11/D3) were 0.8578–0.9795 and 0.8510–0.9717. Aceclofenac alone or co-administered with JOINS was safe and well tolerated with no serious adverse drug reactions or significant differences in the severity of adverse events (AEs) between the two treatment groups. We conclude that co-administration of aceclofenac with JOINS does not influence the PK and safety profiles of aceclofenac.
Subject(s)
Adult , Humans , Drug Interactions , Drug-Related Side Effects and Adverse Reactions , Healthy Volunteers , Korea , Osteoarthritis, Knee , Pharmacokinetics , Plasma , VolunteersABSTRACT
BACKGROUND: Olmesartan medoxomil is an angiotensin II receptor blocker commonly used in hypertension. First objective of this study was to evaluate the bioequivalence of two olmesartan formulations, Olmesartan 20 mg and 40 mg tablet (Yuhan, Pharmaceutical Corp. Seoul, Korea) as test drugs and Olmetec(R) 20 mg and 40 mg tablet (Daewoong, Pharmaceutical Corp. Seoul, Korea) as reference drugs. Second objective of this study was to evaluate the dose-proportionality of two formulations. METHODS: Two studies (20 mg, 40 mg) were conducted as a randomized, open-label, 2-period, crossover design. Each subject received one 20 mg or 40 mg tablet of the reference or test formulation of olmesartan medoxomil in each study. Blood samples were obtained during the 48-hour period after the dose in each treatment period. Wash-out period was 1 week in each study. Concentrations of olmesartan medoxomil in plasma were analyzed using a liquid chromatography system with tandem mass-spectrometric detection (LC/MS/MS). The primary pharmacokinetic parameters were Cmax (maximum concentration) and AUCt (area under the concentration-time curve from time 0 to the last sampling time). RESULTS: A total number of 40 healthy male volunteers participated in the study and 37 volunteers completed both treatment periods in 20 mg trial. All 40 participants completed both treatment periods in 40 mg trial. The 90 % CIs for the geometric mean ratios of the pharmacokinetic parameters (test:reference drug) were 0.93 ~ 1.04 for AUCt and 0.97 ~ 1.08 for Cmax in 20 mg trial. The 90 CIs were 0.94 ~ 1.02 for AUCt and 1.00 ~ 1.11 for Cmax in 40 mg trial. All parameters of two studies satisfy the range of bioequivalence criterion. CONCLUSION: The obtained results indicated that pharmacokinetic exposure to Olmesartan 20 mg and 40 mg tablet was bioequivalent to that of Olmetec(R) 20 mg and 40 mg tablet, respectively.
Subject(s)
Humans , Male , Chromatography, Liquid , Cross-Over Studies , Hypertension , Imidazoles , Plasma , Receptors, Angiotensin , Tetrazoles , Therapeutic EquivalencyABSTRACT
The overall prognosis of acute pyelonephritis is good, but the infections by extended spectrum beta-lactamase (ESBL) producing Escherichia coli (E.coli) cause poor responses to empirical antibiotic treatment, and consequently increase mortality. ESBL can hydrolyze the antibiotics with a beta-lactam ring and confer resistance to oxyimino-cephalosporins and monobactams. If the patient shows poor responses to empirical antibiotics or severe septic conditions, physicians must switch the antibiotics to other antibiotics covering resistant strains without delay. We report a case of acute pyelonephritis by extended-spectrum beta-lactamase producing E.coli in a 29-year-old woman who was empirically treated with oral ciprofloxacin as an initial treatment, but progressed to sepsis.
Subject(s)
Adult , Female , Humans , Anti-Bacterial Agents , beta-Lactamases , Ciprofloxacin , Escherichia , Escherichia coli , Monobactams , Prognosis , Pyelonephritis , SepsisABSTRACT
The overall prognosis of acute pyelonephritis is good, but the infections by extended spectrum beta-lactamase (ESBL) producing Escherichia coli (E.coli) cause poor responses to empirical antibiotic treatment, and consequently increase mortality. ESBL can hydrolyze the antibiotics with a beta-lactam ring and confer resistance to oxyimino-cephalosporins and monobactams. If the patient shows poor responses to empirical antibiotics or severe septic conditions, physicians must switch the antibiotics to other antibiotics covering resistant strains without delay. We report a case of acute pyelonephritis by extended-spectrum beta-lactamase producing E.coli in a 29-year-old woman who was empirically treated with oral ciprofloxacin as an initial treatment, but progressed to sepsis.
Subject(s)
Adult , Female , Humans , Anti-Bacterial Agents , beta-Lactamases , Ciprofloxacin , Escherichia , Escherichia coli , Monobactams , Prognosis , Pyelonephritis , SepsisABSTRACT
PURPOSE: Pandemic influenza A (H1N1) virus has spread rapidly and prompt diagnosis is needed for successful treatment and prevention of transmission. We investigated clinical predictors, validated the use of previous criteria with laboratory tests, and evaluated the clinical criteria for H1N1 infection in the Korean population. MATERIALS AND METHODS: We analyzed clinical and laboratory evaluation data from outpatient clinics at Severance Hospital in Seoul, Korea between November 11 and December 5, 2009. RESULTS: This analysis included a total of 828 patients. Of these, 372 (44.9%) patients were confirmed with H1N1 infection by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). The most common and predictive symptom was cough (90.3%, OR 8.87, 95% CI 5.89-13.38) and about 40% of H1N1-positive patients were afebrile. The best predictive model of H1N1 infection was cough plus fever or myalgia. The sensitivities, specificities, positive predictive values, and negative predictive values of our suggested criteria were 73.9%, 69.5%, 66.4%, and 76.6%, respectively. CONCLUSION: Cough was the most common independent symptom in patients with laboratory-confirmed H1N1 infection, and while not perfect, the combination of cough plus fever or myalgia is suggested as clinical diagnostic criteria. Health care providers in Korea should suspect a cough without fever to be an early symptom of H1N1 infection.
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Influenza A Virus, H1N1 Subtype/metabolism , Influenza, Human/diagnosis , Pandemics , Predictive Value of Tests , Republic of Korea , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and SpecificityABSTRACT
OBJECTIVES: Several studies have found a significant association between the presence of earlobe crease (ELC) and cardiovascular disease (CVD). Brachial-ankle Pulse Wave Velocity (baPWV) is a non-invasive and useful measure of arterial stiffness predicting cardiovascular events and mortality. However, few studies have reported the relationship between ELC and baPWV as a new measure of arterial stiffness. The purpose of this study was to determine whether ELC is related to baPWV in non-diabetic, non-hypertensive, and apparently healthy Korean adults. METHODS: A cross-sectional study was conducted on 573 non-hypertensive, non-diabetic Korean adults aged 20-80 yr. Subjects were stratified into three groups according to gender and menopausal status. baPWV was measured by an automatic waveform analyser. The association between ELC and baPWV was assessed by multiple linear regression analysis after adjusting for conventional cardiovascular disease risk factors including age, gender, blood pressure, lipid profile, and smoking status etc. RESULTS: The overall frequency of ELC was 19.02% and the subjects with ELC showed significantly higher mean baPWV (p<0.0001). Multiple linear regression of subjects revealed that the presence of ELC was independently associated with baPWV (male, p<0.0001; premenopausal female p=0.0162; postmenopausal female p=0.0208). CONCLUSION: ELC had a significant correlation with baPWV, independently controlling for other classical cardiovascular risk factors in adults aged 20 yr or older. ELC is an important surrogate marker of increased arterial stiffness as measured by baPWV in Korean adults.
Subject(s)
Adult , Aged , Female , Humans , Blood Pressure , Cardiovascular Diseases , Cross-Sectional Studies , Korea , Linear Models , Pulse Wave Analysis , Risk Factors , Smoke , Smoking , Vascular Stiffness , BiomarkersABSTRACT
BACKGROUND: Incidentally discovered gallbladder polyp in a health check-up has been increasing in numbers due to the extended use of ultrasonography. Past research has reported on the relationship between body mass index and gallbladder (GB) polyp. As there has been a recent rise in the prevalence of obesity, this research attempted to study GB polyp prevalence and the trend according to time elapse in Korea. METHODS: Retrospective cross sectional research was carried out from the data of Korean Association of Health Promotion, between January 2, 2003 to August 3, 2007 in the subjects who received abdominal ultrasonography. The subjectrs excluded were those below 20 years of age, non-Asian and those who have received cholecystectomy. The number of eligible subjects were 137,135, where 69,493 were males and 67,642 were females. RESULTS: Out of 137,135 subjects, the number of subjects with GB polyp were 5,278, where 3,163 were males and 2,115 were females. According to 2005 census, the age adjusted prevalence was 3.7% (3,656 per 100,000). The prevalence for males was 4,403 per 100,000 (4.4%) and for females 2,943 per 100,000 (2.9%). The prevalence has been increasing for the past five years. CONCLUSION: The prevalence of GB polyp in Korea was found to be higher than the pre-existing reports and the prevalence was higher in males than females. The prevalence is on the increase and there is a need to be more attentive to this issue in the future.