• Korean Journal of Clinical Pharmacy
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• v.1 no.1
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• pp.31-36
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• 1991

Tobramycin is one of the most frequently selected agents for pharmacokinetic drug monitoring because of its narrow therapeutic index and essential role for the management of serious infections, especially gram-negative infections. Its pharmacokinetic parameters are dependent on race, sex, age, ideal body weight. disease states, and etc. Therefore, to schedule the dosing of tobramycin, the individual pharmacokinetic parameters such as half-life and volume of distribution are needed. However, these pharmacokinetic parameters have never been reported in Koreans. The purposes of this study were to evaluate the volume of distribution of tobramycin in cancer patients who had normal renal function, to compare the mean values of Vd reported in the literature, and to compare the measured half-life with the expected half-life based on ABW, LBW, and IBW, respectively. Venous blood samples were collected just before and thirty minutes after dosing during steady state. Serum tobramycin concentrations were determined by $TD_x$ (fluorescence immunoassay). IBW were measured by the method of Devine: and LBW were measured by the method of Hallynck. Creatinine clearances (CLcr) of the patients were estimated using the Cockcroft and Gault equation. Elimination rate constants (kel) were determined using the Welling and Craig equation. Infusion rate (ko), volume of distribution (Vd), and half-life $(t_{1/2})$ were determined using the Saw chuk and Zaske equation. The volume of distribution Was $27\%$ greater than the Schentag's study (0.26 vs 0.33 l/kg), but the half-life was similar to the Levy's study. The predicted half-lives based on IBW were the closest to actual half-lives (1.85 vs 2.01 hr).

• Toxicological Research
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• v.26 no.3
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• pp.217-222
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• 2010

Many studies have reported that bleomycin, anti-cancer drug, induces pulmonary fibrosis as a side effect. However, few investigations have focused on the dose-response effects of bleomycin on pulmonary fibrosis. Therefore, in the present study, we investigated the effects of different doses of bleomycin in male mice. ICR mice were given 3 consecutive doses of bleomycin: 1, 2, or 4 mg/kg in bleomycin-treated (BT) groups and saline only in vehicle control (VC) groups. The animals were sacrificed at 7 and 24 days postinstillation. The severity of pulmonary fibrosis was evaluated according to inflammatory cell count and lactate dehydrogenase (LDH) activity in the broncho alveolar lavage fluid (BALF), and lung tissues were histologically evaluated after hematoxylin and eosin (H&E), and Masson's trichrome staining. BT groups exhibited changed cellular profiles in BAL fluid compared to the VC group, which had an increased number of total cells, neutrophils, and lymphocytes and a modest increase in the number of macrophages at 7 days post-bleomycin instillation. Moreover, BT groups showed a dose-dependent increase in LDH levels and inflammatory cell counts. However, at 24 days after treatment, collagen deposition, interstitial thickening, and granulomatous lesions were observed in the alveolar spaces in addition to a decrease in inflammatory cells. These results indicate that pulmonary fibrosis induced by 4 mg/kg bleomycin was more severe than that induced by 1 or 2 mg/kg. These data will be utilized in experimental animal models and as basic data to evaluate therapeutic candidates through non-invasive monitoring using the pulmonary fibrosis mouse model established in this study.

• Quality Improvement in Health Care
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• v.7 no.2
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• pp.168-179
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• 2000

Background : Economic evaluation of clinical pharmacokinetic consultation services for theophylline, which is being widely used recently, is considered in patients for both proper care and cost efficiency. Mathods : This is a cost-benefit analysis of clinical pharmacokinetic consultation service for theophylline. Trial groups were chosen from 2 general hospitals which was performing clinical pharmacokinetic consultation- services in 1998. Control group was chosen from another one general hospital. The analysis includes 25 patients (sample patients) for trial group and 17 patients for control group. Results : On the basis of incremental analysis, it is estimated that the total (direct and indirect) annual costs of the clinical, pharmacokinetic services of theophylline for the patients in the trial group was about \65 million, whereas total annual benefits from those services was estimated to be about \551 million. The net benefits incurred to the sample patients, thus calculated, was about \485 million per year. In the analysis, we assumed that indirect benefits accruing to those services were non-existent. If that amount was included, the estimated net benefits would be much greater than the calculated one. Conclusion : We found that clinical pharmacokinetic consultation services for theophylline could produce more marginal benefits than marginal costs by those services from the social point of view. More controlled prospective trial in the future would be helpful for affirmation of the results of this study.

• Food Science and Preservation
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• v.24 no.4
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• pp.524-528
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• 2017

Ricinus communis, belongs to the family Euphorbiaceae, has been known as medicinal plants for treatment of inflammation, tumors, antidiabetic, hepatoprotective and laxative. Compared to many pharmacological studies, the effect of R. communis extract on regulating adipogenesis as therapeutic drug for treating obesity has not been reported. R. communis extract (RCE) was investigated to determine its effects on the adipogenesis by monitoring the status of $Wnt/{\beta}-catenin$ signaling and factors involving the differentiation of adipocytes. The differentiation of 3T3-L1 cells monitored by Oil Red O staining was inhibited in concentration dependent manner by RCE. The luciferase activity of HEK 293-TOP cells containing pTOPFlash with Tcf4 response element-luciferase gene was increased approximately 2-folds by the treatment of RCE at concentrations of $100{\mu}g/mL$ compared to the control. Activation of the $Wnt/{\beta}-catenin$ pathway by RCE was further confirmed by immunocytochemical analysis which shows an increment of nuclear localization of ${\beta}-catenin$. In addition, safety of RCE was verified through performing neural stem cell morphology assay. Among the identified flavonoids in RCE, isoquercitrin was the most abundant. Therefore, these results indicate that the adipocyte differentiation was significantly reduced by isoquercitrin in R. communis. In this study, RCE suppresses the adipogenesis of 3T3-L1 cells via the activation of $Wnt/{\beta}-catenin$ signaling.

• Journal of Ginseng Research
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• v.34 no.1
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• pp.8-16
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• 2010

Attention deficit hyperactivity disorder (ADHD) affects 4-12% of chool-age children worldwide and is characterized by three core symptoms: hyperactivity, inattention, and impulsivity. Although standard pharmacological treatments, such as methylphenidate and atomoxetine, are available, concerns about drug-induced psychological and cardiovascular problems, as well as growth retardation and sleep disturbances, highlight the continuing need for new therapeutic interventions. Using a neonatal hypoxia-induced hyperactivity model in rats, the potential positive role that oral administration of red ginseng extract may have in relation to the hyperactive phenotype was investigated. Hypoxia was induced in 2-day-old male Sprague-Dawley (SD) rat pups by placing them in a nitrogen chamber for 15 min. The neonatal hypoxia-induced rats showed a significant increase in hyperactivity phenotype, such as increased movement duration, movement distance, and rearing frequency, which was determined by monitoring their spontaneous locomotor activity using the Ethovision video tracking system. One week of oral treatment with red ginseng extract decreased the hyperactivity phenotype of the neonatal hypoxia-induced rats and increased the locomotor activity of the control rats. In the neonatal hypoxia-induced rats, expression of the norepinephrine transporter in the forebrain was increased, and red ginseng treatment partially prevented its up-regulation, while increasing its level in the control rats. Taken together, these results suggest that red ginseng extract decreased the neonatal hypoxia-induced hyperactivity phenotype, although it increased locomotor activity in normal animals.

• YAKHAK HOEJI
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• v.42 no.5
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• pp.473-479
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• 1998

Lovastatin (LOVA), a fungal metabolite isolated from cultures of Aspergillus terreus, is a competitive HMG-CoA reductase inhibitor used for the treatment of primary hyper cholesterolemia, and has also been shown to suppress growth in a variety of non-glioma tumor cell lines. A sensitive reversed-phase high-perfonnance liquid chromatographic method with ultraviolet (UV) absorbance detection has been developed to quantitate LOVA in human plasma and urine samples using liquid-liquid extraction procedure. Baseline separation of LOVA and internal standard, simvastatin was achieved on a Novapak $C_{18}$ analytical column with a mobile phase containing 0.025M $NaH_2PO_4$: CAN (35:65, v/v%), adjusted pH to 4.5. The flow rate was set at 1.5ml/min, and the column effluent was monitored by a UV detection at 238nm. The limit of quantification was determined to be 0.5${\mu}$g/ml while extraction efficiency of LOVA ranged from 73.4-82.9% at LOVA concentrations of 0.5 to 10${\mu}$g/ml. Good linearity with correlation coefficients greater than 0.999 was obtained in the range of LOVA concentrations from 0.5 to 10${\mu}$g/ml. The accuracy and the precision were proven excellent with relative standard deviation (RSD, %) and relative error (RE, %) of less than 4.2 and 4.0, respectively. Intraday precision, evaluated at five LOVA concentrations (0.5, 1, 2, 5, 10${\mu}$g/ml) and expressed as RSD ranged from 0-1.82% while the interday precision at the same concentrations ranged from 0.7-10.5%. The analytical method described was then successfully employed for the determination of LOVA concentrations in plasma samples obtained during a phase II clinical trial using high doses of LOVA (30-40mg/kg/day). This method could be further utilized for the ongoing pharmacolkinetic studies and therapeutic drug monitoring of the high-dose LOVA therapy in adenocarcinoma patients.

• Biomolecules & Therapeutics
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• v.27 no.2
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• pp.193-200
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• 2019

Ceramide metabolism is known to be an essential etiology for various diseases, such as atopic dermatitis and Gaucher disease. Glucosylceramide synthase (GCS) is a key enzyme for the synthesis of glucosylceramide (GlcCer), which is a main ceramide metabolism pathway in mammalian cells. In this article, we developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to determine GCS activity using synthetic non-natural sphingolipid C8-ceramide as a substrate. The reaction products, C8-GlcCer for GCS, could be separated on a C18 column by reverse-phase high-performance liquid chromatography (HPLC). Quantification was conducted using the multiple reaction monitoring (MRM) mode to monitor the precursor-to-product ion transitions of m/z $588.6{\rightarrow}264.4$ for C8-GlcCer at positive ionization mode. The calibration curve was established over the range of 0.625-160 ng/mL, and the correlation coefficient was larger than 0.999. This method was successfully applied to detect GCS in the human hepatocellular carcinoma cell line (HepG2 cells) and mouse peripheral blood mononuclear cells. We also evaluated the inhibition degree of a known GCS inhibitor 1-phenyl-2-decanoylamino-3-morpholino-1-propanol (PDMP) on GCS enzymatic activity and proved that this method could be successfully applied to GCS inhibitor screening of preventive and therapeutic drugs for ceramide metabolism diseases, such as atopic dermatitis and Gaucher disease.

• Korean Journal of Clinical Pharmacy
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• v.33 no.3
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• pp.195-201
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• 2023

Background: Hematocrit is usually measured from venous blood collected by invasive venipuncture. This study was performed to determine hematocrit accurately and precisely using minimally invasive volumetric absorptive microsampling (VAMS) technique. Such technique is to be applied to determining hematocrit in various clinical settings for the care, including therapeutic drug monitoring, of neonatal or epileptic patients, or patients with high risk of infection or bleeding. Methods: The study was performed using 31 VAMS samples obtained from 21 pancreatic cancer patients. Hematocrit was determined using the values of potassium concentrations obtained from blood in VAMS tips (Hct_VAMS). Hct_VAMS was compared with hematocrit measured from blood collected by venipuncture (Hct_VP). The accuracy and precision of Hct_VAMS in comparison to Hct_VP were evaluated using Bland-Altman plot, Deming regression and mountain plot. Results: Bland-Altman plot displayed a random scattering pattern of the differences between Hct_VAMS and Hct_VP with the mean bias of -0.010 and the 95% limit of agreement ranging from -0.063 to 0.044. Deming regression for Hct_VAMS and Hct_VP line demonstrated very small proportional and constant biases of 1.04 and -0.003, respectively. Mountain plot exhibited a narrow and symmetrical distribution of the differences with their median of -0.011 and central 95% range from -0.049 to 0.033. Conclusion: Hematocrit was accurately and precisely determined using less invasive VAMS technique. Such technique appears to be applicable to determining hematocrit in situations that venipuncture is not favorable or possible.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.2
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• pp.121-127
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• 2024

Vancomycin is a frequently used antibiotic in intensive care units, and the patient's renal clearance affects the pharmacokinetic characteristics of vancomycin. Several advantages have been reported for vancomycin continuous intravenous infusion, but studies on continuous dosing regimens based on patients' renal clearance are insufficient. The aim of this study was to develop a vancomycin serum concentration prediction model by factoring in a patient's renal clearance. Children admitted to our institution between July 1, 2021, and July 31, 2022 with records of continuous infusion of vancomycin were included in the study. Sex, age, height, weight, vancomycin dose by weight, interval from the start of vancomycin administration to the time of therapeutic drug monitoring sampling, and vancomycin serum concentrations were analyzed with the linear regression analysis of the mixed effect model. Univariable regression analysis was performed using the vancomycin serum concentration as a dependent variable. It showed that vancomycin dose (p < 0.001) and serum creatinine (p = 0.007) were factors that had the most impact on vancomycin serum concentration. Vancomycin serum concentration was affected by vancomycin dose (p < 0.001) and serum creatinine (p = 0.001) with statistical significance, and a multivariable regression model was obtained as follows: Vancomycin serum concentration (mg/l) = -1.296 + 0.281 × vancomycin dose (mg/kg) + 20.458 × serum creatinine (mg/dl) (adjusted coefficient of determination, R² = 0.66). This prediction model is expected to contribute to establishing an optimal continuous infusion regimen for vancomycin.

• Parasites, Hosts and Diseases
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• v.54 no.3
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• pp.291-299
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• 2016

Human hydatid disease (cystic echinococcosis, CE) is a chronic parasitic infection caused by the larval stage of the cestode Echinococcus granulosus. As the disease mainly affects the liver, approximately 70% of all identified CE cases are detected in this organ. Optical molecular imaging (OMI), a noninvasive imaging technique, has never been used in vivo with the specific molecular markers of CE. Thus, we aimed to construct an in vivo fluorescent imaging mouse model of CE to locate and quantify the presence of the parasites within the liver noninvasively. Drug-treated protoscolices were monitored after marking by JC-1 dye in in vitro and in vivo studies. This work describes for the first time the successful construction of an in vivo model of E. granulosus in a small living experimental animal to achieve dynamic monitoring and observation of multiple time points of the infection course. Using this model, we quantified and analyzed labeled protoscolices based on the intensities of their red and green fluorescence. Interestingly, the ratio of red to green fluorescence intensity not only revealed the location of protoscolices but also determined the viability of the parasites in vivo and in vivo tests. The noninvasive imaging model proposed in this work will be further studied for long-term detection and observation and may potentially be widely utilized in susceptibility testing and therapeutic effect evaluation.