• Journal of Pharmaceutical Investigation
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• v.39 no.1
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• pp.65-71
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• 2009

The aim of the present study was to evaluate the bioequivalence of two domperidone maleate tablets, Motilium-$M^{(R)}$ Tablet (Janssen Korea Ltd., reference product) and $Toriem^{(R)}$ Tablet (Daewon Pharm. Co., Ltd., test product). Domperidone was extracted by liquid-liquid extraction using tert-butyl methyl ether and separated in less than 3 min on $C_{18}$ reverse-phase column using an isocratic elution. A tandem mass spectrometer, as detector, was used for quantitative analysis in positive mode by a multiple reaction monitoring mode to monitor the m/z $426.1{\rightarrow}119.1$ and the m/z $837.4{\rightarrow}158.2$ transitions for domperidone and the internal standard (roxithromycin), respectively. Calibration curves, from $0.05{\sim}50$ ng/mL of domperidone, showed correlation coefficients (r) higher than 0.9941. Intra day and inter day precision (C.V. %) for quality control were ranged from 10.04 to 16.09% and from 10.87 to 18.69%, respectively. The lower limit of quantification (LLOQ) of domperidone was 0.05 ng/mL. The method described is precise and sensitive and has been successfully applied to the study of bioequivalence of domperidone in 24 healthy Korean volunteers. Twenty-four healthy male Korean volunteers received a single dose of each medicine ($2{\times}12.72\;mg$ domperidone maleate) in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. Plasma concentrations of domperidone were monitored for over a period of 24 hr after the administration. $AUC_{0-t}$ (the area under the plasma concentration-time curve) was calculated by the linear trapezoidal rule. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma concentration-time data. The 90% confidence intervals for the log transformed data were within acceptable range of log 0.8 to log 1.25 (e.g., $log\;0.92{\sim}log\;1.05$ for $AUC_{0-t}$, $log\;0.81{\sim}log\;1.05$ for $C_{max}$). The major parameters, $AUC_{0-t}$ and $C_{max}$ met the criteria of KFDA for bioequivalence indicating that $Toriem^{(R)}$ tablet is bioequivalent to Motilium-$M^{(R)}$ tablet.

• Journal of Pharmaceutical Investigation
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• v.40 no.3
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• pp.175-180
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• 2010

Albumin-modification has been viewed as one of the most effective ways of extending the short in vivo lifetimes of peptide drugs by delaying glomerular filtration. In this study, we describe a new type 2 anti-diabetic exendin-4 (Ex4) peptide derivative with significant binding ability to human serum albumin (HSA). This exendin-4 derivative consists of a 4-branched polyethylene glycol $(PEG)_{5k}$ (Mw: 20 kDa) modified with three stearylamines ($C_{18}-NH_2$) and one exendin-4 on its branches. PEG and stearylamine were selected to provide functionality to increase molecular size and bind to albumin, respectively. This derivative ($3C_{18}-4PEG_{5k}$-Ex4) was shown to have larger molecular size (Ca. 152 kDa) than actual (25.0 kDa) when subjected to size-exclusion chromatography, and the fluorescein-tagged $3C_{18}-4PEG_{5k}$-Ex4 displayed significant binding to the HSA-immobilized Sepharose CL-4B resin using confocal laser scanning microscopy. Furthermore, $3C_{18}-4PEG_{5k}$-Ex4 was found to have acceptable anti-hyperglycemic efficacy via three consecutive oral glucose tolerance testings (OGTT) in fasted type 2 diabetic db/db mice. The $HD_{total}$ value ($57.6{\pm}12.3%$) of $3C_{18}-4PEG_{5k}$-Ex4 at a 50 nmol/kg dose was 2-fold greater than that ($31.0{\pm}8.7%$) of native exendin-4 in non-fasted db/db mice. Especially, the blood glucose levels in the mice group treated with $3C_{18}-4PEG_{5k}$-Ex4 did not rebound to ~150 mg/dL until 24 h after the injection, which obviously shows the extended hypoglycemia. We believe that this derivative has great pharmaceutical potential as a novel long-acting type 2 anti-diabetic injection treatment.

• The Journal of the Korean life insurance medical association
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• v.2 no.1
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• pp.34-36
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• 1985

Korea is an endemic area of chronic hepatitis in the world. Liver cirrhosis and liver cell carcinoma, presumed to be related to such chronic hepatitis, are the major causes of death in this country. The purpose of this study is disclosing the sources of chronic hepatitis in Korea establishing its histologic characteristics, disclosing the patterns of progression in chronic hepatitis, delineating its prognosis and finally speculating its etiology. The study group was composed of 183 patients with biopsy-proven acute icteric viral hepaticis, 32 patients with biopsy- proven anicteric hepatitis and 260 patients with biopsy- proven chronic hepatitis. These patients submitted to long-term follow-up by means of liver needle biopsy and/or clinicolaboratory evaluation. The period of follow-up ranged from two months to 18 years. The histological features of the initial biopsy specimens of chronic hepatitis permitted a division of the cases cases into the following five types: Type I. Persisting portal hepatitis : so called persisting hepatitis 43 Type II. Chronic inactive hepatitis with incomplete strand septal fibrosis. This type has thin fibrotic septation in addition to Type I with portal sclerosis 38 Type III. Chronic active periportal hepatitis(CAPH) : so called aggressive hepatitis, characterized by marked piecemeal necrosis. This type has been subdivided further into three groups: AB and C on the basis of histologic features. A CAPH without cirrhosis 15 B CAPH with cirrhosis 99 C CAPH with diffuse acinus type parenchymal nodules; characterized by rosette-forming micronodules 21 Type IV. Subacute hepatic necrosis; characterized by multilobular and/or bridging necrosis. 14 Type V. Persisting lobular hepatitis; characterized by spotty necrosis, which looks very similar to acute viral hepatitis. Such histologic changes should be persisted for more than six months 30 In Korea the main source of chronic hepatitis is the anicteric type. Of the chronic hepatitis observed in the hospital, Type IIIb was the most frequent in its incidence and occasionally exhibited development of hepatocellular carcinoma, but the mortality was highest in Type IIIc during the period of follow-up. Histologic characteristics of these five types suggest a spectrum of chronic hepatitis in Korea from an early and mild stage to advanced and fatal cirrhosis, which is occasionally associated with primary hepatic cell carcinoma. It seems that Type IV can be followed by flare-up of various stages of acute and chronic hepatitis with HBsAg and that many cases of liver cirrhosis prevalent in Korea occur through such an active process of Type IV. The etiology is not established, but in Korea it is mainly related to HBsAg.

• Quality Improvement in Health Care
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• v.1 no.1
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• pp.44-54
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• 1994

A drug use evaluation (DUE) program has been defined as an "authorized a quality assurance process designed to ensure that drugs are used appropriately, safely, and effectively". A retrospective DUE study on ceftazidime has been conducted by reviewing patients charts following criteria for drug use evaluation established by Am.S.Hosp.Pharm. Total 60 charts of patient treated with ceftazidime in Seoul National University Hospital from Jan. 1.1993 to July.31.1993 were retrospectively reviewed. As a result, 44 cases(73%) were met with the criteria for the justification of use. In analysing process indicators including culture and sensitivity test, CBC, LFT, history of anaphylaxis monitoring before initial dose, vital sign monitoring were relatively well documented showing the accepted level above 80%, while appropriated dose were infrequently documented with low accepted level. In outcome analysis, blood culture after discontinuing drug were rarely documented, with accepted level of 46%. For using effectively and safely, ceftazidime is recommended to be administrated to optimal indication, and monitored actively for preventing adverse effect.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2263-2268
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• 2015

Background: Many studies have reported associations of the X-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphism with colorectal cancer (CRC) risk, but the results remained controversial. Hence, we performed the present meta-analysis with different inheritance models. Materials and Methods: We searched the PubMed and Google scholar databases for studies relating to associations between XRCC3 Thr241Met polymorphism and risk of CRC. 16 studies with 5,193 cases and 6,645 controls were finally included into the meta-analysis. Results: We found that the XRCC3 Thr241Met polymorphism was associated with increased CRC risk only under a dominant genetic model (CC+CT vs. TT: OR 0.575, 95%CI 0.498-1.665, p<0.001, $P_{heterogeneity}=0.00$, $I^2=83%$). There was a significant association between XRCC3 Thr241Met polymorphism and CRC risk in Caucasian in the overall 8 studies under only in the heterozygote genetic model (CT vs. TT: OR=0.929, 95%CI =0.806-1.070, P=0.308, $P_{heterogeneity}=0.002$, $I^2=57%$). Four studies evaluated the XRCC3 Thr241Met polymorphism and CRC risk in Asians. Two genetic models of the XRCC3 polymorphism were significantly correlated with increasing risk in Asians (dominant model: CC+CT vs. TT: OR= 0.609, 95%CI=411-0.902, P=0.013, $P_{heterogeneity}=0.54$, $I^2=0.00%$; Allele model: C vs. T: OR=0.708, 95 %=CI 0.605-0.829, p=0.000, $P_{heterogeneity}=0.000$, $I^2=92%$). The sensitivity analysis suggested stability of this meta-analysis and no publication bias was detected. Conclusions: In conclusion, this meta-analysis indicates that XRCC3 Thr241Met shows an increased CRC risk, particularly in Asians rather than Caucasians.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2771-2774
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• 2012

Aim: Tumors of upper gastrointestinal tract are among the cancers that have a quite lethal course. Cytotoxic chemotherapy is the most efficient therapeutic modality for metastatic gastric cancer. In patients who do not respond to first-line treatment, the response rate to second-line therapies is generally low and the toxicity rates high. This study concerned the efficacy and the side effect profile of second-line therapy with irinotecan in the patients who were being followed-up with the diagnosis of metastatic gastric cancer in $\dot{I}$zmir, Turkey. Materials and Methods: We retrospectively evaluated the efficacy and toxicity in 31 patients with metastatic gastric adenocarcinoma who presented to the polyclinic of Medical Oncology of Izmir Ataturk Education and Research Hospital between May 2008 and July 2011. All received chemotherapy regimens containing cisplatin, fluoropyrimidine (5-FU) and docetaxel as the first-line therapy for late stage disease. Irinotecan as a single agent was given at a dose of 210 mg/$m^2$ on each 21 days. Irinotecan (180 mg/$m^2$ on day 1), 5-FU (500 mg/$m^2$ on days 1-2) and leucovorin (LV; 60 mg/$m^2$ on days 1-2) as a combined regimen were given over a 14 day period. Results: Median age was 54 (range, 31-70). Irinotecan was given as a combined regimen for median 6 cycles (range, 3-12) and as a single agent for median 3 cycles (range, 1-10). Metastases were detected in one site in six patients (19%), in two different sites in 17 patients (55%) and in three or more sites in eight patients (26%). Four patients (12.9%) showed partial response and six patients (19.3%) showed stable disease. Progression-free survival (PFS) was found to be 3.26 months (95% CI, 2.3-4.2). Median overall survival (OS) was found to be 8.76 months (95% CI, 4.5-12.9). The most commonly seen grade 3/4 side effect was neutropenia but the the therapy was generally well-tolerated. Conclusions: In this study, it was demonstrated that second-line therapy with irinotecan given following the first-line therapy with cisplatin, fluoropyrimidine (5-FU) and docetaxel was efficient and safe. Further studies are needed for confirmation.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6649-6655
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• 2014

Radiation therapy is an important treatment for head and neck squamous cell carcinoma (HNSCC). However, how to promote radiation sensitivity in HNSCC remains a challenge. This study aimed to investigate the radiosensitizing effects of fenofibrate on HNSCC and explore the underlying mechanisms. HNSCC cell lines CNE-2 and KB were subjected to ionizing radiation (IR), in the presence or absence of fenofibrate treatment. Cell growth and survival, apoptosis and cell cycle were evaluated. In addition, CNE-2 cells were xenografted into nude mice and subjected to IR and/or fenofibrate treatment. The expression of cyclinB and CDK1 was detected by Western blotting. Our results showed that fenofibrate efficiently radiosensitized HNSCC cells and xenografts in mice, and induced apoptosis and G2/M arrest via reducing the activity of the CDK1/cyclinB1 kinase complex. These data suggest that fenofibrate could be a promising radiosensitizer for HNSCC radiotherapy.

• Journal of the Korean Arthroscopy Society
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• v.3 no.2
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• pp.132-137
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• 1999

Displaced tibial spine fractures need the anatomical reduction of the displaced bone fragment to achieve normal range of motion and anterior stability of the knee joint. The purpose of this paper is to describe details of arthroscopic technique using suture hook and pull-out PDS and to evaluate the clinical results. We report 7 cases who underwent arthroscopic reduction and internal fixation using suture hook and pull-out PDS. All cases had fresh fractures generated within 3 weeks. The follow up period was at average 16.6 months. The fracture union was achieved at average 7.4 weeks. Knee exercise was started 2 weeks after the operation. One of the patients, who had combined injury of posterior cruciate ligament and lateral meniscus, showed limitation of knee movement. But he was underwent the arthroscopic fibrolysis at one year later, he returned to normal range of motion. Arthroscopic treatment of displaced tibial spine fracture using suture hook and pull-out PDS showed good results including rigid fixation and early mobilization. Therefore it is thought to be one of the effective operative techniques in treatment of the tibial spine fractures.

• Journal of Pharmaceutical Investigation
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• v.35 no.5
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• pp.323-328
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• 2005

The purpose of the present study was to evaluate the bioequivalence of two torasemide tablets, Torem tablet (Roche Korea Co., Ltd., Korea, reference drug) and Boryung Torsemide tablet (Boryung Pharmaceutical Co., Ltd., Korea, test drug), according to the guidelines of Korea Food and Drug Administration (KFDA). After adding an internal standard (furosemide) to human serum, serum samples were extracted using 5 mL of ethyl acetate. Compounds were analyzed by reverse-phase HPLC method with UV detection. This method showed linear response over the concentration range of 0.05 ug/mL with correlation coefficient of 0.999. The lower limit of quantitation using 0.5 mL of serum was 0.05 ug/mL which was sensitive enough for pharmacokinetic studies. Twenty-eight healthy male Korean volunteers received each medicine at the torasemide dose of 20 mg in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. Serum concentrations of torasemide were monitored by an HPLC-UV for over a period of 12 hr after the administration. $AUC_{t}$(the area under the serum concentration-time curve from time zero to 12 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (maximum serum drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the serum concentration-time data. Analysis of variance was carried out using logarithmically transformed $AUC_{t}$ and $C_{max}$. No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90% confidence intervals of the $AUC_{t}$ ratio and the $C_{max}$ ratio for Boryung Torsemide/Torem were log 0.97-10g 1.03 and log 0.93log 1.12, respectively. These values were within the acceptable bioequivalence intervals of log 0.80-log 1.25. Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating Boryung Torsemide tablet and Torem tablet are bioequivalent.

• Applied Biological Chemistry
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• v.51 no.2
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• pp.148-152
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• 2008

This study was to elucidate the effect of low dose gamma (${\gamma}$)-ray irradiation on the germination, seedling growth and antioxidant activity in sunflower seeds. The seed germination was stimulated in the range of 2.7${\sim}$8.0% by low dose ${\gamma}$-ray irradiation compared with that of the control; however, the germination of seeds stored for 4 months after irradiated was decreased at all low dose ${\gamma}$-ray irradiation groups. Especially, the germination rate of 32 Gy-irradiated seed group was much lower than that of the other groups and 8 Gy was the optimal radiation dose for germination at room temperature. Though there was variation with storage time and temperature, seedling growth stored at 10$^{\circ}C$ for 4 months after irradiated was promoted at the 1 Gy ${\gamma}$-ray irradiation group compared to seed stored at 25$^{\circ}C$. For the antioxidant activity of ${\gamma}$-ray irradiated seeds extract, 4 Gy and 32 Gy groups were significantly increased by 68.83% and 95.44%, respectively, compared to control at the concentration of 100 ${\mu}g$/ml.