Cancer patients with neutropenic septic shock: etiology and antimicrobial resistance

Background/Aims@#Among patients with febrile neutropenia that developed after chemotherapy, high-risk patients, such as those having clinical instability or Multinational Association of Supportive Care in Cancer score of < 21, require hospitalization for intravenous empiric antibiotic therapy. Monotherapy with an anti-pseudomonal ß-lactam agent is recommended. Although many studies reported the microbial etiology of infections and resistant patterns of febrile neutropenia, the patients were not well characterized as having neutropenic septic shock. Therefore, this study aimed to determine the microbial spectrum of infections and resistance patterns of their isolates in patients with chemotherapy-induced neutropenic septic shock. @*Methods@#Data of adult patients diagnosed with neutropenic septic shock in the emergency department between June 2012 and December 2016 were extracted from a prospectively compiled septic shock registry at a single academic medical center. Thereafter, microbiological studies and antimicrobial susceptibility tests were conducted. @*Results@#In total, 109 bacteria were found in patients with neutropenic septic shock. Gram-negative bacteria were the predominant causative organisms (84, 77.1%). Moreover, 33 microorganisms (30.3%) were multidrug-resistant (MDR) bacteria with extended-spectrum ß-lactamase-producing Escherichia coli (17, 50%) being the commonest. The most commonly affected sites in patients with MDR bacterial infections were the gastrointestinal tract (45%) and unknown (43.5%). Approximately 48.5% of MDR bacteria were resistant to cefepime but not to piperacillin- tazobactam or carbapenem. @*Conclusions@#MDR bacteria were prevalent in patients with chemotherapy-induced neutropenic septic shock. Therefore, piperacillin-tazobactam or carbapenem may be considered as empiric antibiotics if MDR bacteria are suspected to be causative agents.

Characteristics of orbital wall fractures in preschool and school-aged children

OBJECTIVE: This study aimed to evaluate the injury patterns in pediatric patients with an orbital wall fracture (OWF) and to identify the differences in injury patterns between preschool and school-aged patients with OWF who presented to the emergency department. METHODS: We performed a retrospective observational study in the emergency department of a tertiary hospital between January 2004 and March 2014. A total of 177 pediatric patients (7 years) pediatric groups. RESULTS: The inferior wall was the most common fracture site in both the preschool and school-aged pediatric groups (50.0% vs. 64.4%, P=0.15). The male-to-female ratio and the mechanism of injury showed significant differences between the two age groups. Violence was the most common mechanism of injury in the school-aged pediatric group (49.3%), whereas falls from a height caused OWF in approximately half of the patients in the preschool pediatric group (42.9%). Concomitant injuries and facial fractures had a tendency to occur more frequently in the school-aged pediatric group. CONCLUSION: Significant differences according to the sex and mechanisms of injury were identified in preschool and school-aged pediatric patients with OWF.

Rapid Collection of Opinions from Healthcare Professionals in Multiple Institutions Using Short Message Service and Google Forms / 대한의료정보학회지

No abstract available.

Post lumbar puncture headache: Case report of a serious adverse event in first-in-human study

A lumbar puncture can be used to measure the concentrations of drugs and/or pharmacodynamic biomarkers during clinical trials of central nervous system drugs. We report a case of a post lumbar puncture headache (PLPH) in a first-in-human study, which was reported as a serious adverse event. A 20-year-old man received 200 mg of the investigational product (IP) for 7 days and underwent a lumbar puncture for cerebrospinal fluid sampling before IP administration (Day 1, pre-dose) and after 7 days and multiple IP administrations (Day 7, 1 hour post-dose). After discharge on Day 8, the subject complained of headache, nausea, vomiting, neck stiffness, and numbness of the extremities. The symptoms occurred when he got up and disappeared after he remained in the supine position for several minutes. Five days later, he visited the neurology clinic of the main hospital. The neurologist recommended hospitalization for further evaluation and symptom management, and the subject was then admitted to the hospital. There were no abnormal findings in vital signs, laboratory results, or brain-computed tomography. His symptoms disappeared during the hospitalization period. It was important to distinguish whether the headache was IP-related or lumbar puncture-related. Therefore, knowledge of clinical characteristics and differential diagnosis of PLPH is paramount. Furthermore, if severe PLPH occurs, a consultation with a neurologist and imaging studies should be considered for a differential diagnosis of PLPH.

Can Glasgow-Blatchford Score and Pre-endoscopic Rockall Score Predict the Occurrence of Hypotension in Initially Normotensive Patients with Non-variceal Upper Gastrointestinal Bleeding? / 대한소화기학회지

BACKGROUND/AIMS: The aim of this study was to identify the ability of Glasgow-Blatchford score (GBS) and pre-endoscopic Rockall score (pre-E RS) to predict the occurrence of hypotension in patients with non-variceal upper gastrointestinal bleeding who are initially normotensive at emergency department. METHODS: Retrospective observational study was conducted at Asan Medical Center emergency department (ED) in patients who presented with non-variceal upper gastrointestinal bleeding from January 1, 2011 to December 31, 2013. Study population was divided according to the development of hypotension, and demographics, comorbidities, and laboratory findings were compared. GBS and pre-E RS were estimated to predict the occurrence of hypotension. RESULTS: A total of 747 patients with non-variceal upper gastrointestinal bleeding were included during the study period, and 120 (16.1%) patients developed hypotesion within 24 hours after ED admission. The median values GBS and pre-E RS were statistically different according to the occurrence of hypotension (8.0 vs. 10.0, 2.0 vs. 3.0, respectively; p<0.001). In the receiver operating characteristic curve analysis of hypotension development, the area under the curve of GBS and pre-E RS were 66% and 64%, respectively. The sensitivity and the specificity of GBS using optimal cut-off value were 81% and 46%, respectively, while those based on the pre-E RS were 74% and 46%, respectively. CONCLUSIONS: GBS and pre-E RS were both not sufficient for predicting the occurrence of hypotension in non-variceal upper gastrointestinal bleeding. Development of other scoring systems are needed.

Early Antibiotic Administration and Mortality in Patients with Septic Shock in Emergency Department

PURPOSE: The Surviving Sepsis Campaign recommend initiating broad spectrum antibiotics within the first hour of recognition of septic shock. An unknown proportion of the effectiveness of earlier antibiotics administration will remain in septic shock patients treated with an early quantitative resuscitation in emergency department (ED). We were to compare the 28-day mortality between earlier antibiotic administration (< or =1 hour) and early antibiotic administration (1 hour to 6 hour) in septic shock patients in ED. METHODS: A total of 536 consecutive septic shock patients were prospectively collected from January 2010 to June 2012. We identified 357 patients who were developed shock at initial assessment, and measured the time of initial antibiotics administration. The primary outcome was 28-day mortality. RESULTS: Mean age was 62.8+/-13.7 years old and 222 patients were male (62.2%). The median time from shock recognition-to-antibiotics administration was 94.0 min (IQR 47.0-150.0) and 28-day mortality rate was 20.2%. When the relationship of 28-day mortality between earlier antibiotic administration (< or =1 hour) and early antibiotic administration (1 hour to 6 hour) was compared, no significant difference was shown (19.5% vs. 20.5%, p=0.82). CONCLUSION: Earlier antibiotics administration may have no additional outcome value in septic shock patients treated with an early quantitative resuscitation in ED.

Clinical Characteristics and Predictive Factors of Septic Shock in Patients with Pyogenic Liver Abscess

PURPOSE: The aim of this study was to describe clinical, biochemical, and radiologic features in patients with pyogenic liver abscess and to investigate predictors of septic shock. METHODS: We consecutively included subjects who were diagnosed as pyogenic liver abscess in the emergency department (ED) from January 1st, 2010 to June 30th, 2013. Through review of medical records, clinical, biochemical, and radiologic data were collected. The primary endpoint was septic shock during hospitalization. RESULTS: A total of 228 patients were included, with a mean age of 60.8+/-12.8 years, and 63.2% were men. Among them, 198 patients presented with fever and GCS or =120/min, respiratory rate > or = 22/min, body temperature (BT) > or =38degrees C, WBC, platelet, BUN, creatinine, albumin, AST, alkaline phosphatase (ALP), Creactive protein (CRP), abscess size > or =5 cm, and bilobal involvement were significantly associated with septic shock (p or =38degrees C (OR 1.95, 1.36-2.78), BUN (OR 1.03, 1.01-1.06), ALP (OR 1.003, 1.000-1.005), and abscess size > or =5 cm (OR 2.31, 1.08-4.94) were independent predictors of septic shock. CONCLUSION: Low Systolic Bp, High Bt, Elevated Bun And Alp, And Abscess Size > or =5 Cm Were Independently Associated With Septic Shock In Patients With Pyogenic Liver Abscess.

Clinical Characteristics of 372 Cases of Transient Global Amnesia in the Emergency Department: A Single Center Study

PURPOSE: Transient global amnesia (TGA) is characterized by abrupt onset of antegrade amnesia usually seeking emergency care. We analyzed the clinical characteristics of TGA patients and the significance of diffusion weighted imaging (DWI) in the diagnosis of TGA. METHODS: Retrospective analysis was performed using electronic medical records of patients diagnosed as TGA in the emergency departments from January 2003 to December 2013. The patient's clinical characteristics and precipitants were analyzed, and detection rate of hippocampal lesion was compared according to the time to DWI after symptom onset (24 h). RESULTS: Of 372 consecutive TGA patients studied, 27 had a positive DWI lesion in hippocampus. Demographics and vascular risk profile were not significantly different between those in DWI (+) and DWI (-), and neither was duration of amnesia (p=0.076). However, the median time interval to DWI was significantly longer in DWI (+) than DWI (-) [7.5 (5.5~15.0) h vs. 6.0 (3.5~9.0) h, p=0.011]. In addition, the detection rate of hippocampal lesion increased with the time interval [0-6 h (4.1%), 6~12 h (10.7%), 12~24 h (11.1%), and >24 h (16.1%), p=0.004]. CONCLUSION: Positive hippocampal lesion on DWI can confirm the diagnosis of TGA; however, difference in lesion detectability in regard to time interval from symptom onset to DWI should be considered in diagnosis of TGA with DWI.

Methemoglobinemia Caused by an Inert Ingredient after Intentional Ingestion of Pesticide / 대한구급학회지

We report two cases of toxic methemoglobinemia caused by an inert ingredient in pesticide product after intentional ingestion of pesticide. First, 51-year-old male visited to the emergency department (ED) after the ingestion of pesticide in a suicide attempt. Initial methemoglobin (MetHb) level was 25.6%. We did not know the cause of methemoglobinemia at that time. Second, 56-year-old female visited to the ED after the ingestion of the same pesticide in a suicide attempt. MetHb level after 30 minutes was 16.1%. The patients were treated with methylene blue. We contacted to the Korean Rural Development Administration and estimated that magnesium nitrate was more likely to cause methemoglobinemia. This report highlights the importance of considering the possibility of methemoglobinemia caused by inert ingredient in pesticide and early antidotal therapy.

Quantification of Human Plasma-Busulfan Concentration by Liquid Chromatography-Tandem Mass Spectrometry

BACKGROUND: Busulfan, an alkylating agent administered prior to hematopoietic stem cell transplantation, has a narrow therapeutic range and wide variability in metabolism. We developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for rapid and accurate quantification of plasma busulfan. METHODS: Busulfan was separated and detected using an LC system containing a C18 column equipped with MS/MS. The sample was eluted with a mobile phase gradient for a total run time of 10 min. Plasma busulfan concentration was quantified against a 6-point standard curve in a multiple reaction monitoring mode at mass-to-charge (m/z) 264.1 > 151.1. Precision, recovery, matrix effect, linearity, detection capability, carryover, and stability were evaluated. The range of plasma busulfan concentration was obtained by analyzing samples from 9 children receiving busulfan. RESULTS: The coefficients of variation of within-run and within-laboratory precision were all below 5%. Recoveries were all within the range of 100-105%. Linearity was verified from 0 to 5,000 ng/mL. Limit of detection and limit of quantification were 1.56 and 25 ng/mL, respectively. Carryover rate was within allowable limits. Plasma busulfan concentration was stable for 2 weeks at -20degrees C and -80degrees C, but decreased by 25% when the plasma was stored for 24 hr at room temperature, and by <5% in 24 hr at 4degrees C. The plasma busulfan concentrations were between 347 ng/mL and 5,076 ng/mL. CONCLUSIONS: Our method using LC-MS/MS enables highly accurate, reproducible, and rapid busulfan monitoring with minimal sample preparation. The method may also enable safe and proper dosage.

Methemoglobinemia Caused by an Inert Ingredient after Intentional Ingestion of Pesticide / 대한중환자의학회지

We report two cases of toxic methemoglobinemia caused by an inert ingredient in pesticide product after intentional ingestion of pesticide. First, 51-year-old male visited to the emergency department (ED) after the ingestion of pesticide in a suicide attempt. Initial methemoglobin (MetHb) level was 25.6%. We did not know the cause of methemoglobinemia at that time. Second, 56-year-old female visited to the ED after the ingestion of the same pesticide in a suicide attempt. MetHb level after 30 minutes was 16.1%. The patients were treated with methylene blue. We contacted to the Korean Rural Development Administration and estimated that magnesium nitrate was more likely to cause methemoglobinemia. This report highlights the importance of considering the possibility of methemoglobinemia caused by inert ingredient in pesticide and early antidotal therapy.

Genetic Polymorphisms of the Carboxylesterase 1 (CES1) Gene in a Korean Population

Human carboxylesterase 1 (CES1) is a serine esterase that hydrolyzes various exogenous compounds. Single nucleotide polymorphisms (SNPs) of CES1 may lead to inter-individual metabolic variability of its substrates. The allele and haplotype frequencies of known SNPs have been demonstrated to vary among ethnic groups. We analyzed genetic variations of CES1 in a Korean population. Direct sequencing of all exons and flanking regions of the CES1 gene was performed on samples obtained from 200 Koreans. We identified 41 SNPs. The most frequent SNPs was -914G>C (frequency: 99.5%), followed by 4256G>A (frequency: 65.8%), -75T>G (frequency: 59.3%). Haplotype analysis using the identified SNPs revealed fifteen haplotypes (> or =1% haplotype frequency) in our samples. The most frequent haplotype was Hap1 (frequency: 15.4%). Among the identified 41 SNPs, nine of which are novel variants and 14 SNPs were nonsynonymous variants. Using the functional predictive software PolyPhen-2, the G19V, E221G, and A270S variants were predicted to be most likely damaging to the function and structure of CES1. In-vitro analyses for two of these variants have been previously performed; however, functional evaluation of E221G (11657A>G, rs200707504) still needs to be conducted. Therefore, further studies are warranted to characterize the functional impact of E221G on CES1 activity.

Hospital disaster plan and disaster medicine

In general, the disaster rescue team should do their work within 1 to 2 hours after disaster, and disaster medical assistance team (DMAT) should care the victims at disaster site within 3 to 6 hours. Since about 10 years ago, world health organization, world meteorological organization, and world congress of disaster emergency medicine emphasized that each countries should complete the disaster plan on 'chemical, biological, radiological, nuclear, explosives' (CBRNE) disaster. After these warnings, the most of countries has strengthened the hospital disaster plan, and also organized disaster services system such as DMAT, hazardous material information system, and others. In Korea, the most of tertiary hospitals can not operate hospital disaster plan effectively, and the government did not support hospitals on disaster plan politically and financially. As a result, only a small number of hospitals is operating DMAT, and a few hospital completed CBRNE disaster preparedness such as disaster drill, personal protective equipments, decontamination set. The poison information center that control information on hazardous material is not established yet, and most physicians can not get information on chemicals, biologics and other hazardous materials when CBRNE disaster occur. To operate effective disaster plan, each hospitals should modernize the disaster plan on internal disaster, external disaster, and CBRNE disaster. The government should support hospitals to keep DMAT and special preparedness on CBRNE disaster. When CBRNE disaster strikes, the poison information center should expand their capability to provide information on the various kinds of hazardous materials.

Kind and Estimated Stocking Amount of Antidotes for Initial Treatment for Acute Poisoning at Emergency Medical Centers in Korea

Antidotes for toxicological emergencies can be life-saving. However, there is no nationwide estimation of the antidotes stocking amount in Korea. This study tried to estimate the quantities of stocking antidotes at emergency department (ED). An expert panel of clinical toxicologists made a list of 18 emergency antidotes. The quantity was estimated by comparing the antidote utilization frequency in a multicenter epidemiological study and the nation-wide EDs' data of National Emergency Department Information System (NEDIS). In an epidemiological study of 11 nationwide EDs from January 2009 to December 2010, only 92 (1.9%) patients had been administered emergency antidotes except activated charcoal among 4,870 cases of acute adult poisoning patients. Comparing with NEDIS data, about 1,400,000 patients visited the 124 EDs nationwide due to acute poisoning and about 103,348 adult doses of the 18 emergency antidotes may be required considering poisoning severity score. Of these, 13,224 (1.9%) adult doses of emergency antidotes (575 of atropine, 144 of calcium gluconate or other calcium salts, 2,587 of flumazenil, 3,450 of N-acetylcysteine, 5,893 of pralidoxime, 287 of hydroxocobalamin, 144 of sodium nitrite, and 144 of sodium thiosulfate) would be needed for maintaining the present level of initial treatment with emergency antidotes at EDs in Korea.

Validation of the Blatchford Bleeding Score in Cancer Patients with Upper Gastrointestinal Bleeding

PURPOSE: The Glasgow Blatchford Score (GBS) and the Rockall score are validated risk tools for predicting adverse outcomes in patients with upper gastrointestinal bleeding (UGIB). In this study, we attempted to validate these risk assessment tools in patients with active cancer who visited an emergency department (ED) with UGIB. METHODS: We retrospectively reviewed electronic medical records of patients with active cancer presented to Asan Medical Center ED from January 2009 to December 2011. The primary outcomes required therapeutic interventions (transfusion, endoscopic/surgical/radiologic interventions), and there was a recurrence of bleeding or mortality within 30 days. RESULTS: Of the 225 patients, 197(87.6%) needed interventions. The area under the receiver-operator curves showed that the GBS [0.86; 95% Confidence Interval (CI), 0.77-0.95] surpassed the clinical Rockall (0.67; 95% CI, 0.55-0.79) and full Rockall scores (0.72; 95% CI, 0.61-0.83) in predicting clinical interventions. Regarding a score of 2 or less as negative, the GBS showed a sensitivity of 0.99 and a specificity of 0.54. When patients were divided according to their source of bleeding, the sensitivity and specificity did not change. CONCLUSION: The GBS outperformed clinical and full Rockall scores in predicting the intervention in patients with active cancer. The source of bleeding was not an important factor in the score's performance. The GBS also showed very good sensitivity; however, its specificity is suboptimal and limits its role as a sole indicator for decisions in cancer patients with UGIB.

The Experiences of the Emergency Antidote Stock and Delivery Service by the Korean Poison Information Center

PURPOSE: Antidotes for toxicological emergencies can be life-saving. However, there is no nationwide stocking and delivery system for emergency antidotes in Korea. We report on a two-year experience of a nationwide stocking and delivery trial for emergency antidotes at emergency departments in Korea. METHODS: An expert panel of clinical toxicologists reviewed and made a list of 15 stocked antidote. These antidotes were purchased or imported from other countries and delivered from 14 antidote stocking hospitals nationwide 24 hours per day, seven days per week. RESULTS: From August 1, 2011 to April 30, 2013, 177 patients with acute poisoning, with a median age of 48.5 years, were administered emergency antidotes. The causes of poisoning were intentional in 52.0% and 88.0% were intentional as a suicide attempt. Regarding clinical severity, using the poisoning severity score, 40.7% of patients had severe to fatal poisoning and 39.0% had moderate poisoning according to clinical severity. The most frequent presenting symptom was neurologic deficit, such as altered mentality (62.7%). alerted mentality (62.7%). Emergency antidotes were administered as follows: methylene blue (49 cases), flumazenil (31), N-acetylcysteine (25), glucagon (17), 100% ethanol (15), cyanide antidote kit (12), anti-venin immunoglobulin (5), pyridoxine (4), hydroxocobalamine (2), and deferoxamine (1). The median time interval from antidote request to delivery at the patient's bedside was 95 minutes (interquartile range 58.8-125.8). CONCLUSION: Findings of this study demonstrated the possibility of successful operation of the nationwide system of emergency antidotes stocking and delivery in Korea.

Value of Cardiac Biomarkers for Predicting Hypotension in Non-high-risk Patients with Acute Pulmonary Embolism

PURPOSE: Recent and numerous studies have indicated that cardiac biomarker elevation during acute pulmonary embolism (PE) predicts in-hospital death. However, the role of cardiac biomarkers for predicting the occurrence of hypotension is unknown. The aim of the present study was to evaluate whether increased levels of cardiac biomarkers can predict the occurrence of hypotension (sytolic blood pressure (SBP) 0.05 ng/mL) upon admission were an independent predictor for developing hypotension within 24 hours in patients with stable acute PE at the time of ED admission (odds ratio 11.0, 95% confidence interval (CI) 2.8-43.8, p=0.00). CONCLUSION: In stable patients with acute PE, an elevated TnI can predict the in-hospital development of hypotension within 24 hours. This finding is valuable for selecting patients who might benefit from intensive clinical surveillance and escalated treatment.

The Clinical Value of TnI and BNP for the Evaluation of Sepsis-related Cardiac Dysfunction in the Emergency Department

PURPOSE: Acute cardiac dysfunction is a well recognized manifestation of organ failure in severe sepsis and septic shock. Although echocardiography is the golden standard for the evaluation of cardiac dysfunction, it is difficult to use in the emergency department (ED). The purpose of this study was to determine the availability of cardiac biomarkers for the estimation of cardiac dysfunction in septic shock patients. METHODS: All study subjects included consecutive patients with septic shock diagnosed in the ED and treated with an algorithm of early goal-directed therapy between January 2011 and June 2012. We enrolled patients measured for cardiac biomarkers and performed echocardiography within 24 hours. We divided patients into two groups based on the occurrence of left ventricular dysfunction (defined as an ejection fraction< or =40%) and compared serum levels of troponin-I (TnI) and B-type natriuretic peptide (BNP) between the two groups. The area under the receiver operating characteristic (ROC) curve was used to compare the diagnostic ability of TnI and BNP. RESULTS: A total of 127 patients with septic shock and evaluated for cardiac dysfunction were enrolled in this study. TnI and BNP were significantly higher in the left ventricular dysfunction group group (4.2+/-9.0 vs. 0.6+/-1.8 ng/mL, respectively, p<0.05) compared with the non-dysfunction group (1087.6+/-680.1 vs. 633.2+/-859.1 pg/mL, respectively, p<0.05). However, in the ROC curve for predicting left ventricular dysfunction, the area under the curves of TnI and BNP, respectively, were 0.631(95% CI 0.473-0.788, p=0.103) and 0.704 (95% CI 0.552-0.856, p=0.011). TnI and BNP showed a 84.6% negative predictive value. CONCLUSION: Although TnI and BNP were significantly higher in septic shock patients with cardiac dysfunction but demonstrated limited accuracy compared to echocardiography. However, TnI and BNP have high negative predictive value in septic shock patients for the evaluation of cardiac dysfunction. Therefore they could serve as a valuable supplement for the detection of cardiac dysfunction.

Clinical Analysis of Patients with Cardiotoxicity Caused by Himalayan Mad Honey

PURPOSE: The aim of this study was to evaluate the clinical characteristics and outcome of patients who presented to the emergency department (ED) with cardiotoxicity caused by ingestion of Himalayan mad honey. METHODS: Medical records of 12 patients who presented to the ED from January 1, 2005 to December 31, 2012 with cardiotoxicity caused by ingestion of Himalayan mad honey were retrospectively reviewed. RESULTS: The mean age of patients was 54.5 years and 58.3% were men. The median amount of mad honey ingested was 30.0 cc, and the mean time from ingestion to onset of symptoms was 39.4 minutes. All patients had hypotension and bradycardia upon arrival in the ED. The initial electrocardiogram showed sinus bradycardia in seven patients, junctional bradycardia in four patients, and atrial fibrillation with slow ventricular response in one patient. Four patients were treated with intravenous normal saline solution only. Eight patients were treated with intravenous normal saline solution and atropine sulfate in a dose ranging from 0.5 to 2.0 mg. Blood pressure and pulse rate returned to normal limits within 24 hours in all patients. CONCLUSION: Our study showed that all patients with cardiotoxicity caused by ingestion of Himalayan mad honey had severe hypotension, bradycardia, and bradyarrythmias, including sinus bradycardia and junctional bradycardia and all patients responded well to conservative treatment, including intravenous normal saline solution and intravenous atropine sulfate.

Pharmacokinetic Characteristics of Cefcapene Pivoxil Hydrochloride after Single Oral Administration in Healthy Korean Subjects

BACKGROUND: Cefcapene pivoxil hydrochloride (CFPN-PI) is an oral ester cephalosporin antibiotic with a broad spectrum. In this study, we investigated the pharmacokinetics (PK) and tolerability of CFPN-PI following single oral administration in healthy Korean subjects. METHODS: An open label, dose escalation, parallel group study was conducted in 18 healthy male volunteers. A single dose of CFPN-PI was administered to 6 subjects in each treatment group of 100, 150 and 200 mg. Serial blood and urine samples were collected up to 12 h and 24 h after dosing, respectively. Plasma and urine concentrations of cefcapene were measured by HPLC-UV. PK parameters were estimated using non-compartmental analysis. For the safety evaluation, adverse event monitoring, clinical laboratory tests and physical examination were performed throughout the study. RESULTS: Median values of time to peak plasma concentration were observed around 1.5 to 2.0 h. Maximum plasma concentrations (Cmax) were 1.04 +/- 0.22, 1.24 +/- 0.46 and 1.56 +/- 0.43 mg/L (mean +/- SD), and area under the plasma concentration time curve (AUCinf) were 2.94 +/- 0.46, 3.97 +/- 1.28 and 4.70 +/- 1.19 h*mg/L in 100, 150 and 200 mg dose groups, respectively. The differences of dose normalized Cmax and AUCinf among three groups were not statistically significant. The fractions of drug excreted in urine unchanged were 31.5 % - 42.9 %. There were no serious adverse events or clinically significant abnormalities related to CFPN-PI. CONCLUSION: CFPN-PI was well tolerated with single oral administration and showed a linear PK property within 100 - 200 mg in healthy Korean male subjects.