1.Evaluation of pharmacokinetic drugdrug interaction between tegoprazan and clarithromycin in healthy subjects
Minkyung OH ; Heechan LEE ; Seokuee KIM ; Bongtae KIM ; Geun Seog SONG ; Jae-Gook SHIN ; Jong-Lyul GHIM
Translational and Clinical Pharmacology 2023;31(2):114-123
Tegoprazan is a novel potassium-competitive acid blocker that treats gastric acid-related diseases. Clarithromycin was widely used as one of various regimens for eradicating Helicobacter pylori. This study compared the pharmacokinetic and safety profile of tegoprazan and clarithromycin between combination therapy and monotherapy to evaluate the potential drug-drug interaction. An open-label, randomized, 6-sequence, 3-period crossover study was conducted in 24 healthy subjects. According to the assigned sequence, the subject was administered the assigned treatment during 5 days in each period. PK parameters of tegoprazan and clarithromycin administered in combination were compared with those of the respective monotherapies. The co-administration of tegoprazan with clarithromycin increased maximum steady-state plasma concentration (C ss,max ) and area under the plasma concentration-time curve in dosing interval at steady-state (AUC ss,tau ) of tegoprazan (1.6-fold in C ss,max and 2.5-fold in AUC ss,tau ) and M1 (2.0-fold in C ss,max , 2.5-fold in AUC ss,tau ) than tegoprazan alone. The C ss,max and AUC sss,tau of 14-hydroxyclarithromycin increased 1.8- and 2.0-fold in co-administration, respectively. The AUC ss.tau of clarithromycin was slightly increased in co-administration, but C ss,max was not changed. Combination of tegoprazan and clarithromycin and those of the respective monotherapies were tolerated in 24 healthy subjects. There may exist drug interaction that lead to reciprocal increase in plasma drug concentrations when tegoprazan and clarithromycin were administrated in combination and no safety concerns were raised. It is suggested that an in-depth analysis of the concentrationresponse relationship is necessary to determine whether these concentration changes warrant clinical action.
2.Experience with Mechanical Circulatory Support for Medically Intractable Low Cardiac Output in a Pediatric Intensive Care Unit.
Jung Bin PARK ; Jae Gun KWAK ; Hong Gook LIM ; Woong Han KIM ; Jeong Ryul LEE ; Yong Jin KIM
Korean Circulation Journal 2017;47(4):490-500
BACKGROUND AND OBJECTIVES: Mechanical circulatory support with extracorporeal membrane oxygenation (ECMO) and ventricular assist device has always been the optimal choice for treating the majority of medically intractable low cardiac output case. We retrospectively investigated our institution's outcomes and variables associated with a high risk of mortality. SUBJECTS AND METHODS: From 1999 to 2014, 86 patients who were of pediatric age or had grown-up congenital heart disease underwent mechanical circulatory support for medically intractable low cardiac output in our pediatric intensive care unit. Of these, 9 grown-up congenital heart disease patients were over 18 years of age, and the median age of the subject group was 5.82 years (range: 1 day to 41.6 years). A review of all demographic, clinical, and surgical data and survival analysis were performed. RESULTS: A total of 45 (52.3%) patients were successfully weaned from the mechanical assist device, and 25 (29.1%) survivors were able to be discharged. There was no significant difference in results between patients over 18 years and under 18 years of age. Risk factors for mortality were younger age (<30 days), functional single ventricle anatomy, support after cardiac operations, longer support duration, and deteriorated pre-ECMO status (severe metabolic acidosis and increased levels of lactate, creatinine, bilirubin, or liver enzyme). The survival rate has improved since 2010 (from 25% before 2010 to 35% after 2010), when we introduced an upgraded oxygenator, activated heart transplantation, and also began to apply ECMO before the end-stage of cardiac dysfunction, even though we could not reveal significant correlations between survival rate and changed strategies associated with ECMO. CONCLUSION: Mechanical circulatory support has played a critical role and has had a dramatic effect on survival in patients with medically intractable heart failure, particularly in recent years. Meticulous monitoring of acid-base status, laboratory findings, and early and liberal applications are recommended to improve outcomes without critical complication rates, particularly in neonates with single ventricle physiology.
Acidosis
;
Bilirubin
;
Cardiac Output, Low*
;
Creatinine
;
Critical Care*
;
Extracorporeal Membrane Oxygenation
;
Heart Defects, Congenital
;
Heart Failure
;
Heart Transplantation
;
Heart-Assist Devices
;
Humans
;
Infant, Newborn
;
Intensive Care Units*
;
Lactic Acid
;
Liver
;
Mortality
;
Oxygen
;
Oxygenators
;
Physiology
;
Resuscitation
;
Retrospective Studies
;
Risk Factors
;
Survival Rate
;
Survivors
3.Community-acquired Escherichia coli Enteritis in Korean Children: The Clinical Application of a Stool Polymerase Chain Reaction Assay.
Youie KIM ; Hyo Jin KIM ; Sooyeon LIM ; Kil Seong BAE ; Seung Beom HAN ; Dae Chul JEONG ; Jin Han KANG ; Gook Jae SHIN ; Gun Dong LEE ; Yeon Joon PARK
Infection and Chemotherapy 2017;49(4):275-281
BACKGROUND: Although Escherichia coli is a common cause of bacterial enteritis in Korea, reports on community-acquired E. coli enteritis in Korean children are scarce. This study aimed to determine the clinical characteristics and pathotype distribution of community-acquired E. coli enteritis diagnosed by a multiplex polymerase chain reaction (PCR) assay in Korean children. MATERIALS AND METHODS: The medical records of children aged 18 years or less who were diagnosed with acute gastroenteritis by the attending physician between 2013 and 2016 were retrospectively reviewed. The clinical characteristics of children diagnosed with E. coli enteritis were investigated and compared with those diagnosed with Salmonella enteritis. E. coli and Salmonella infections were diagnosed by a stool PCR assay. RESULTS: Among 279 children, in whom PCR assays for E. coli and Salmonella spp. were performed, Salmonella enteritis and E. coli enteritis were diagnosed in 43 (15.4%) and 39 (14.0%) children, respectively. Among the 39 children with E. coli enteritis, enteropathogenic E. coli (n=21, 53.8%) and enteroaggregative E. coli (n=15, 38.4%) were the most common causative agents. Empirical antibiotics were administered to 33 (84.6%) children. A total of 31 (79.5%) children developed fever, and 25 (80.6%) of them had the fever for 3 days or less, which resolved a median of 1 day (range 0-3 days) after hospitalization. The most frequent gastrointestinal symptom was diarrhea (n=36, 92.3%). Significantly more children with E. coli enteritis were aged 2 years or less as compared with those with Salmonella enteritis (41.0% vs. 21.9%, P = 0.021). Children with Salmonella enteritis more frequently complained of fever (97.7% vs. 79.5%, P = 0.012), abdominal pain (90.7% vs. 64.1%, P = 0.004), and hematochezia (46.5% vs. 10.3%, P < 0.001) than those with E. coli enteritis. Erythrocyte sedimentation rate and C-reactive protein levels were significantly higher in children with Salmonella enteritis than those with E. coli enteritis (P < 0.001). CONCLUSION: Enteropathogenic E. coli was the most frequent pathotype in Korean children with E. coli enteritis that caused mild clinical symptoms. A stool PCR assay for E. coli may be useful for epidemiological purpose and for an early diagnosis of E. coli enteritis.
Abdominal Pain
;
Anti-Bacterial Agents
;
Blood Sedimentation
;
C-Reactive Protein
;
Child*
;
Diarrhea
;
Early Diagnosis
;
Enteritis*
;
Enteropathogenic Escherichia coli
;
Escherichia coli*
;
Escherichia*
;
Fever
;
Gastroenteritis
;
Gastrointestinal Hemorrhage
;
Hospitalization
;
Humans
;
Korea
;
Medical Records
;
Multiplex Polymerase Chain Reaction
;
Polymerase Chain Reaction*
;
Retrospective Studies
;
Salmonella
;
Salmonella Infections
4.Population Pharmacokinetic Analysis of Piperacillin/Tazobactam in Korean Patients with Acute Infections.
Yong Kyun KIM ; Jin Ah JUNG ; Hyang Ki CHOI ; In Gyu BAE ; Won Suk CHOI ; Jian HUR ; Sung Joon JIN ; Shin Woo KIM ; Ki Tae KWON ; Sang Rok LEE ; Jae Gook SHIN ; Sungmin KIEM
Infection and Chemotherapy 2016;48(3):209-215
BACKGROUND: For more effective and safer usage of antibiotics, the dosing strategy should be individualized based on the patients’ characteristics, including race. The aim of this study was to investigate the population pharmacokinetic (PK) profiles of piperacillin and tazobactam in Korean patients with acute infections. MATERIALS AND METHODS: At least four consecutive 2/0.25 g or 4/0.5 g doses of piperacillin/tazobactam (TZP) were intravenously infused over 1 h every 8 h for patients with creatinine clearance (CL(cr)) ≤50 ml/min or CL(cr) >50 mL/min, respectively. Blood samples from 33 patients at a steady-state were taken pre-dose and at 0 min, 30 min, and 4-6 h after the fourth infusion. The population PK analysis was conducted using a non-linear mixed-effects method. A likelihood ratio test was used to select significant covariates, with significance levels of P <0.05 for selection and P <0.01 for elimination. RESULTS: Both piperacillin PK and tazobactam PK were well described by a two-compartment model with first-order elimination. Creatinine clearance and body weight, as covariates on clearance (CL) and volume of central compartment (V1), were selected among the covariates possibly affecting PK parameters of both drugs. CL was defined as CL = 2.9 + 4.03 × CL(cr)/47 for piperacillin and CL = 1.76 + 4.81 × CL(cr)/47 for tazobactam. V1 was defined as V1 = 19.5 × weight/60 for piperacillin and V1 = 22.6 × weight/60 for tazobactam. CONCLUSION: The PK profiles of TZP at a steady-state in Korean patients with acute infections were well described by a two-compartment model with first-order elimination. Both piperacillin and tazobactam clearances were significantly influenced by creatinine clearance.
Anti-Bacterial Agents
;
Body Weight
;
Continental Population Groups
;
Creatinine
;
Humans
;
Methods
;
Piperacillin
5.Low Serum Concentrations of Moxifloxacin, Prothionamide, and Cycloserine on Sputum Conversion in Multi-Drug Resistant TB.
Seung Heon LEE ; Kyung Ah SEO ; Young Min LEE ; Hyun Kyung LEE ; Je Hyeong KIM ; Chol SHIN ; Jong Ryul GHIM ; Jae Gook SHIN ; Dong Hyun KIM
Yonsei Medical Journal 2015;56(4):961-967
PURPOSE: Low serum concentrations of drugs used to treat multi-drug resistant tuberculosis (MDR-TB) have occasionally been associated with treatment failure. We determined the frequencies of low serum concentrations of anti-MDR-TB drugs, and assessed the effects of these concentrations on 2-month sputum conversion. MATERIALS AND METHODS: The serum levels of moxifloxacin (MF), prothionamide (PTH), and cycloserine (CS) were determined for 89 serum samples by high-pressure liquid chromatography-tandem mass spectrometry. RESULTS: Low serum concentrations of MF, PTH, and CS below the minimal levels of the normal ranges were 83.3% (20/24), 59.2% (29/49), and 71.2% (47/66), respectively. There were no significant differences between the 2-month sputum conversion group (n=25) and the 2-month sputum non-conversion group (n=4) in median drug concentrations (microg/mL) of MF (1.46 vs. 1.60), PTH (0.91 vs. 0.70), and CS (14.90 vs. 14.90). However, a poor compliance rate was significantly greater in the 2-month sputum non-conversion group (75.0%, 3/4) than in the 2-month sputum conversion group (0%, 0/25) (p=0.001). CONCLUSION: The frequency of low serum concentrations of anti-MDR-TB drugs was substantial and might not affect the 2-month sputum conversion rate. Larger prospective studies with timely sampling are needed to investigate the role of therapeutic drug monitoring in MDR-TB.
Adult
;
Aged
;
Antitubercular Agents/blood/*pharmacokinetics/therapeutic use
;
Chromatography, High Pressure Liquid
;
Cycloserine/blood/*pharmacokinetics/therapeutic use
;
Fluoroquinolones/blood/*pharmacokinetics/therapeutic use
;
Humans
;
Medication Adherence
;
Middle Aged
;
Prothionamide/blood/*pharmacokinetics/therapeutic use
;
Retrospective Studies
;
Sputum/*microbiology
;
Tandem Mass Spectrometry
;
Tuberculosis, Multidrug-Resistant/blood/*drug therapy
;
Young Adult
6.Genetic polymorphisms of CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 in Vietnamese-Koreans.
Ye Ji LIM ; Eun Young CHA ; Hye Eun JUNG ; Jong Lyul GHIM ; Su Jun LEE ; Eun Young KIM ; Jae Gook SHIN
Translational and Clinical Pharmacology 2014;22(2):70-77
The Vietnamese-Koreans, especially offspring between a Vietnamese mother and a Korean father constituted the highest proportion (64.2%) of total Kosian population according to a census in 2014. To evaluate genetic characteristics in the Vietnamese-Koreans, a total of 25 alleles from CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 were genotyped using SNaPshot method with DNA samples of 127 Vietnamese-Koreans. The previous reports on the CYPs of Korean and Vietnamese populations were also analyzed for the comparative studies for the frequencies of CYP alleles. The statistical significances in allele and genotype frequencies among the ethnics were analyzed by Chi-square or Fisher's exact probability test. Although most of variants analyzed in 5 CYPs did not reach the statistically significant difference between the Vietnamese-Koreans and Vietnamese, some alleles were only found in Vietnamese-Koreans. Compared with Korean population, frequencies of CYP2D6*1 and CYP2D6*10B were statistically different from Vietnamese-Koreans (p<0.05). This is the first report to describe the CYP genotype profiles of Vietnamese-Koreans, which may provide important insight for the genotype based prediction of CYP activities of this admixture of Korean and Vietnamese.
Alleles
;
Asian Continental Ancestry Group
;
Censuses
;
Cytochrome P-450 CYP2D6*
;
Cytochrome P-450 Enzyme System
;
DNA
;
Fathers
;
Genotype
;
Humans
;
Mothers
;
Polymorphism, Genetic*
7.Reconstruction of Distal Phalangeal Soft Tissue Defects with Reverse Homodigital Artery Island Flap.
Byung Gook KIM ; Soo Hong HAN ; Ho Jae LEE ; Soo Hyun LEE
Archives of Reconstructive Microsurgery 2014;23(2):65-69
PURPOSE: Soft tissue reconstruction is essential for recovery of finger function and aesthetics in any traumatic defect. The authors applied a reverse homodigital artery island flap for soft tissue defect on distal part of digits. The aim of this study is to evaluate the efficacy of the procedure. MATERIALS AND METHODS: Seven cases of soft tissue defects of finger tip were included in this study. There were six male and one female, mean age was 43 years and mean follow-up period was 38 months. The length of flaps ranged from 2.0 to 2.5 cm and width ranged from 1.0 to 2.0 cm. Flap survival, postoperative complications were evaluated. RESULTS: All flaps survived without loss. Donor sites were repaired with primary closure in five cases and skin graft in two cases. None of the patients showed significant complications and their average finger motion was 255degrees in total active motion at the last follow-up. CONCLUSION: The authors suggest that the reverse homodigital artery island flap could be a versatile treatment option for the soft tissue defect on distal part of digits.
Arteries*
;
Esthetics
;
Female
;
Fingers
;
Follow-Up Studies
;
Humans
;
Male
;
Postoperative Complications
;
Skin
;
Soft Tissue Injuries
;
Tissue Donors
;
Transplants
8.Four Endoscopic Predictors of Carcinoma as a Final Diagnosis after Endoscopic Resection of Forceps Biopsy-proven Gastric Adenomas.
Jun Young SONG ; Hyung Hun KIM ; Hae Won LEE ; Eun Ju CHO ; Jae Joon HEO ; Gook Hwan JANG ; Seun Ja PARK ; Moo In PARK ; Won MOON ; Hee Kyung JANG
The Korean Journal of Helicobacter and Upper Gastrointestinal Research 2013;13(1):36-43
BACKGROUND/AIMS: Previous studies have reported that the frequency of re-diagnosing as carcinoma after endoscopic resection of gastric adenoma ranges between 6% and 47%. Therefore, specific endoscopic findings have been used to predict re-diagnosing as carcinoma after endoscopic resection of gastric adenoma at our center. We evaluated whether there is a use for these indicators for predicting carcinoma as a final diagnosis in forceps biopsy-proven adenomas. MATERIALS AND METHODS: We investigated 378 tissue samples from 308 patients. Classification of specimens as adenoma and carcinoma was based on postresection specimen. Endoscopic findings were reviewed for tumor location, size, gross appearance, surface nodularity, central concavity, surface color, and presence of ulcers. These variables were analyzed and compared between the adenoma group (275 cases) and the carcinoma group (103 cases), assigned based on post-resection diagnosis. RESULTS: The mean patient age was 61, and 227 of the patients were male. The mean lesion diameter was 14.9+/-8.1 mm in the adenoma group and 17.9+/-9.3 mm in the carcinoma group. A lesion size of 15 mm or greater, depressed appearance, surface nodularity, central concavity, and presence of high-grade dysplasia were all independently associated with re-diagnosing as carcinoma after endoscopic resection. CONCLUSIONS: Lesion size of 15 mm or greater, depressed-type appearance, central concavity, and nodular surface are feasible predictors of carcinoma as a final diagnosis in forceps biopsy-proven adenomas. Physicians need to recommend immediate endoscopic resection for forceps biopsy-proven adenomas with these four independent features so as not to miss the optimal window for treatment.
Adenoma
;
Humans
;
Male
;
Stomach
;
Surgical Instruments
;
Ulcer
9.Four Endoscopic Predictors of Carcinoma as a Final Diagnosis after Endoscopic Resection of Forceps Biopsy-proven Gastric Adenomas.
Jun Young SONG ; Hyung Hun KIM ; Hae Won LEE ; Eun Ju CHO ; Jae Joon HEO ; Gook Hwan JANG ; Seun Ja PARK ; Moo In PARK ; Won MOON ; Hee Kyung JANG
The Korean Journal of Helicobacter and Upper Gastrointestinal Research 2013;13(1):36-43
BACKGROUND/AIMS: Previous studies have reported that the frequency of re-diagnosing as carcinoma after endoscopic resection of gastric adenoma ranges between 6% and 47%. Therefore, specific endoscopic findings have been used to predict re-diagnosing as carcinoma after endoscopic resection of gastric adenoma at our center. We evaluated whether there is a use for these indicators for predicting carcinoma as a final diagnosis in forceps biopsy-proven adenomas. MATERIALS AND METHODS: We investigated 378 tissue samples from 308 patients. Classification of specimens as adenoma and carcinoma was based on postresection specimen. Endoscopic findings were reviewed for tumor location, size, gross appearance, surface nodularity, central concavity, surface color, and presence of ulcers. These variables were analyzed and compared between the adenoma group (275 cases) and the carcinoma group (103 cases), assigned based on post-resection diagnosis. RESULTS: The mean patient age was 61, and 227 of the patients were male. The mean lesion diameter was 14.9+/-8.1 mm in the adenoma group and 17.9+/-9.3 mm in the carcinoma group. A lesion size of 15 mm or greater, depressed appearance, surface nodularity, central concavity, and presence of high-grade dysplasia were all independently associated with re-diagnosing as carcinoma after endoscopic resection. CONCLUSIONS: Lesion size of 15 mm or greater, depressed-type appearance, central concavity, and nodular surface are feasible predictors of carcinoma as a final diagnosis in forceps biopsy-proven adenomas. Physicians need to recommend immediate endoscopic resection for forceps biopsy-proven adenomas with these four independent features so as not to miss the optimal window for treatment.
Adenoma
;
Humans
;
Male
;
Stomach
;
Surgical Instruments
;
Ulcer
10.A Case of Misidentification of Aspergillus versicolor Complex as Scopulariopsis Species Isolated from a Homograft.
Hee Jae HUH ; Jang Ho LEE ; Kyung Sun PARK ; Tae Gook JUN ; I Seok KANG ; Yae Jean KIM ; Chang Seok KI ; Nam Yong LEE
Annals of Clinical Microbiology 2013;16(2):105-109
We report a case of the isolation of the Aspergillus versicolor complex, initially misidentified by morphological characteristics as the Scopulariopsis species, from a homograft with a bicuspidalized pulmonary valve. An eighteen-month-old female, who had critical pulmonary stenosis, underwent pulmonary valve replacement. On postoperative day 8, she developed a fever, which did not respond to empiric broad-spectrum antibiotics. While no definitive source was identified, a filamentous fungus was isolated from the thawed homograft tissue culture prior to implantation on the operation day. The colonies were powdery green with white edges on Sabouraud dextrose agar. Microscopic examination showed septate hyphae with branched conidiophores and chains of spiny conidia, which suggested Scopulariopsis species. After direct sequencing of the internal transcribed spacer (ITS) regions, the fungus was identified as the A. versicolor complex. To our knowledge, the isolation of the A. versicolor complex from a homograft valve has not been previously described. This case shows that laboratory staff should be aware that microscopic morphology of the A. versicolor complex can resemble that of a number of other genera, including Scopulariopsis species.
Agar
;
Anti-Bacterial Agents
;
Aspergillus
;
Bicuspid
;
European Continental Ancestry Group
;
Female
;
Fever
;
Fungi
;
Glucose
;
Humans
;
Hyphae
;
Pulmonary Valve
;
Pulmonary Valve Stenosis
;
Scopulariopsis
;
Spores, Fungal
;
Transplantation, Homologous

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