• 약학회지
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• 제37권6호
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• pp.638-646
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• 1993

A cepfialosporin with an aminothiazoiylmethoxyimino-type side chain at the 7 position and bicyclic quinolone dithicarbamate at the 3' position was synthesized. It has broad and potent antivacterial activity in vitro. The antibacterial spectrum reflects contributions of both the cephalosporin moiety and the quinolone moiety. Thus, this compound was named DACD implying a dualaction cephalosporin derivative. In this paper, the physicochemical proper-ties (lipid-water partition, pKa), stability and pharmacokinetics of DACD were determined and compared with cefotaxime 3'-norfloxacin dithiocarbamate (CENO). Stability tests were studied in pH 1.20, 6.80 and 8.00 buffers and in the presence of AB type human plasma, rat liver homogenate and its .betha.-lactamase. The pharmacokinetic parameters of DACD were evaluated in mice after a single intravenous dose of 40 mg/kg. The results are as follows. The lipid-water partition coefficient of DACD was higher than that of CENO. The calculated pKa values of CENO and DACD, were 6.82$\pm$0.03, 7.53$\pm$0.21, respectively. In the hydrolysis test, half-lives (t$^{1/2}$) of CENO and DACD was 66.0 hr and 80.0 hr in pH 6.80 buffer, 190 hr and 91.4 hr in pH 8.00 buffer. CENO and DACD were rapidly hydrolyzed in human plasma and in rat liver hornogenate. Half-lives (t$_{1/2}$ of CENO and DACD were 1.29 hr and 1.15 hr in hyman plasma, 0.62 hr and 0.71 hr rat liver homogenate. In $\beta$-lactamase stability test, CENO and DACD were very stable to the .betha.-lactamases obtained from three different strains. Half-life (t$_{1/2}$) and areas under the curve (AUC) in mice were 2.33 hr and 15.97 (mg.h/1), respectively.

• Asian Pacific Journal of Cancer Prevention
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• 제17권1호
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• pp.125-129
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• 2016

Background: Patients with differentiated thyroid cancers (DTC) who receive radioactive iodine-131 (RAI) are released from isolation when their dose rate is below the regulatory requirements. The purpose of this study was establish predicting factors for early release from the isolation facility after RAI administration in patients with DTC. Materials and Methods: This was a prospective study which included 96 (58 females and 38 males) patients with DTC who had received RAI from April 2013 till August 2015. The study was duly approved by the ethical committee of the institute. Patients who had complete information of primary tumor size (PTS), serum TSH, stimulated thyroglobulin level [sTg] with antibodies (IU/ml) at the time of RAI treatment were included. All had a normal serum creatinine level. To attain lower effective half-life good hydration and administration of soft laxative were ensured. Dose rate was measured (immediately, 24 h and 36 h) at 1 meter distance from anterior mid trunk and a dose rate <$50{\mu}Sv/h$ was considered as the releasing criterion. At 24 h 50 patients were released while the remaining 46 patients were released at 36 h. A post-ablative whole body scan (PA-WBIS) was performed 5-8 days after RAI ablation in all patients. Results: Patients released after 24 h were significantly younger, had smaller lesions with higher proportion of papillary cancer, lower sTg, lower sTg/TSH ratio and had received a lower dose of RAI as comapred to those who were discharged after 36 h. Serum TSH and gender were not found to have any significant correlation between two cohorts. ROC and multivariate analysis have shown age ${\leq}37years$, PTS ${\leq}3.8cm$, $RAI{\leq}150mCi$, $sTg{\leq}145ng/ml$ and $sTg/TSH{\leq}1.085$ as strong indepedent predictors for early release. Conclusions: We conclude that younger age (${\leq}37years$), smaller tumor size (${\leq}3.8cm$), lower RAI dose (${\leq}150mCi$), lower sTg (${\leq}145ng/ml$) and a lower sTg/TSH ratio (${\leq}1.085$) are significant independent predictors for release at 24 h after RAI treatment in DTC patients. Effective utilization of these factors could help the treating physicians to use limited number of internment facilities with higher throughput, lower cost and lower psychological stress to patients.

• Radiation Oncology Journal
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• 제8권1호
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• pp.115-124
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• 1990

고 에너지 23MV광자선의 특성 중 임상적용에 중요한 심부선량 백분율, 조직-최대선량비 (TMR), 산란-최대선량비 (SMR), 표면선량 및 출력선량 보정계수등의 변수가 이온전리 (IC-10)함 및 평행 평판전리 (PS-033)함에 의해 측정 조사되었다. 명목상의 23 MV X-선에 대한 가속에너지는 $18.5\pm0.5$ MV로 측정되었다. Mevatron KD 8067의 23 MV X-선의 중심선속의 반가층이 기하학적인 좁은 선속으로 측정되었으며 반가층의 두께는 $24.5\;g/cm^2$이었다. 조직-최대선량비는 심부선량백분율표에서 구해졌으며, 실측치와 비교한 결과 각 조사면의 크기와 깊이에서 약간의 차이를 보였으나 평균 $0.7\pm0.5$의 오차를 나타내고 있어 계산에 의한 TMR 값과 잘 일치함을 보였다. 조사면 $0\times0\;cm^2$의 TMR 값은 zero 조사면의 유효감약계수에 의한 값과, 각 조사면의 조직-최대 선량비로 부터 비선형최소자승법에 의해 구해진 유효선흡수계수 및 반가층 측정에 의한 유효선흡수 계수에 의한 값들로 비교되었으며, $\mu=0.0283{\pm}0,0002cm^{-1}$을 보였고, 세 방법 모두 오차범위내에서 잘 일치됨을 보였다. 한편, 불규칙 조사면의 선량계산에 이용될 SMR은 조사면의 반경 50cm까지 계산되어 대형 조사 면에서도 선량율 산출이 이루어지도록 하였다. Mevatron KD 8067의 23 MV X-선의 조직 표면선량은 SSD 100 cm, 1$10\times10\;cm^2$의 조사면에서 최대조직선량율의 $9.6\%,\;25\times25\;cm^2$에서는 $25.4\%$를 보였다.

• Journal of Pharmaceutical Investigation
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• 제39권3호
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• pp.177-183
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• 2009

A rapid and sensitive reversed-phase high performance liquid chromatography (HPLC) method was developed for the determination of piroxicam in the rabbit plasma. After a treatment of plasma sample by liquid-liquid extraction, the drug was analyzed on an HPLC system with ultraviolet detection at 330 nm. HPLC was carried out using reversed-phase isocratic elution with a C18 column, a mobile phase of a mixture of acetonitril, doubly deionized water and acetic acid 43.74:56.00:0.26 v/v%) at a flow rate of 1.1 mL/min. The chromatograms showed good resolution and sensitivity and no interference of plasma. The calibration curve for the drug in plasma sample was linear over the concentration range of 0.01-2.0 ${\mu}$g/mL. The intra- and inter-day assay accuracies of this method ranged from 86.82% to 108.33% of normal values and the precision did not exceed 13% of relative standard deviation. The plasma concentration of piroxicam decreased to below the quantifiable limit at 12 hr after the i.v. bolus administration to rabbits following dose of 0.375 mg/kg yielding a apparen t plasma half life of 1.38 hr. The transdermal route prolongs plasma levels of piroxicam. The bioavailability, calculated from the dose-adjusted ratio of the $AUC_{transdermal}$ to the $AUC_{i.v.}$, was 7.44%. The plasma concentration of piroxicam was detected by 48 hr after the transdermal administration of patch at a dose of 32 mg/kg. This method was suitable for cutaneous absorption studies of piroxicam in the rabbit after transdermal administration of different types of dosages of the drug.

• Biomolecules & Therapeutics
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• 제21권2호
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• pp.170-172
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• 2013

The pyrimidine nucleoside uridine has recently been reported to have a protective effect on cultured human corneal epithelial cells, in an animal model of dry eye and in patients. In this study, we investigate the pharmacokinetic profile of uridine in rabbits, following topical ocular (8 mg/eye), oral (450 mg/kg) and intravenous (100 mg/kg) administration. Blood and urine samples were serially taken, and uridine was measured by high-performance liquid chromatography-tandem mass spectrometry. No symptoms were noted in the animals after uridine treatment. Uridine was not detected in either plasma or urine after topical ocular administration, indicating no systemic exposure to uridine with this treatment route. Following a single intravenous dose, the plasma concentration of uridine showed a bi-exponential decay, with a rapid decline over 10 min, followed by a slow decay with a terminal half-life of $0.36{\pm}0.05$ h. Clearance and volume of distribution were $1.8{\pm}0.6$ L/h/kg and $0.58{\pm}0.32$ L/kg, respectively. The area under the plasma concentration-time curves (AUC) was $59.7{\pm}18.2{\mu}g{\cdot}hr/ml$, and urinary excretion up to 12 hr was ~7.7% of the dose. Plasma uridine reached a peak of $25.8{\pm}4.1{\mu}g/ml$ at $2.3{\pm}0.8$ hr after oral administration. The AUC was $79.0{\pm}13.9{\mu}g{\cdot}hr/ml$, representing ~29.4% of absolute bioavailability. About 1% of the oral dose was excreted in the urine. These results should prove useful in the design of future clinical and nonclinical studies conducted with uridine.

• 대한한의학방제학회지
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• 제15권2호
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• pp.99-111
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• 2007

In the present study, the anti-inflammatory effect of "Jungcheonhwadamgangki-tang ga Antler" water extract was tested in Xylene-Application mouse ear acute inflammation model. The test articles were once dosed before Xylene-Application, and the changes on body weight and ear weights and histopathological observation of induced ear were conducted with ear histomorphometry. The obtained results were as follows. The increases of absolute and relative ear weight detected in vehicle control compared to that of sham, were significantly and dose-dependently inhibited by Jungcheonhwadamgangki-tang ga Antler in the present study. A classic acute inflammatory histological changes such as subcutaneous edema, thickness and infiltration of inflammatory cells, was detected in vehicle control. However, these histological changes were significantly and dose-dependently inhibited by Jungcheonhwadamgangki-tang ga Antler. In addition, the increases of ear thickness half and thickness full detected in the vehicle control were also dose-dependently decreased in the all Jungcheonhwadamgangki-tang ga Antler-dosing groups. Base on these results, it is concluded that Jungcheonhwadamgangki-tang ga Antler extracts has clear anti-inflammatory effect on the acute inflammation such as bronchial asthma.

• Asian Pacific Journal of Cancer Prevention
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• 제15권16호
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• pp.6519-6524
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• 2014

The aim of this study was to evaluate the clinical outcomes of radical cystectomy (RC) and concurrent chemoradiotherapy (CRT) with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) in patients with locally advanced bladder cancer (BC). From December 2000 to February 2012, 72 patients with locally advanced BC (T3-4a, N0 or N+, M0) received either RC or CRT. RC with bilateral pelvic lymph node dissection including the common iliac region as the standard procedure. Patients in the CRT group received one cycle of MVAC followed by radiotherapy with a half dose of MVAC and then two more cycles of MVAC. Standard fractionation at a daily dose of 1.8-2.0 Gy was used, with a median total dose of 50 Gy (range, 45-60 Gy). The 3-year progression-free survival (PFS) rates in the RC and CRT groups were 56.2% and 25.6%, respectively (p=-0.015) and the 3-year overall survival (OS) rates were 63.5% and 48.1% (p=0.272). Multivariate Cox proportional hazards regression analysis with application of a propensity score indicated that RC was a significant predictor of PFS (p=0.033) but not of OS (p=0.291). Among patients with locally advanced BC, PFS was significantly prolonged in the RC group compared with the CRT group. However, RC was not a significant predictor of OS. Although the sample size in this study was small, the results suggest that patient background and postoperative quality of life should be considered when choosing treatment strategy for locally advanced BC.

• Journal of Dental Anesthesia and Pain Medicine
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• 제18권5호
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• pp.295-300
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• 2018

Background: Removal of the plate following Le Fort I osteotomy and BSSO (bilateral sagittal split osteotomy) is a common procedure. However, patients who undergo plate removal experience intense pain and discomfort. This study investigated the half-maximal effective concentration ($Ce_{50}$) of remifentanil in the prevention of plate removal pain under sedation using dexmedetomidine. Methods: The study evaluated 18 patients, between 18 and 35 years of age, scheduled for elective surgery. Remifentanil infusion was initiated after sedation using dexmedetomidine, and started at a dose of 1.5 ng/mL on the first patient via target-controlled infusion (TCI). Patients received a loading dose of $1.0{\mu}g/kg$ dexmedetomidine over 10 min, followed by a maintenance dose of $0.7{\mu}g/kg/h$. When the surgeon removed the plate, the patient Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score was observed. Results: The Ce of remifentanil ranged from 0.9 to 2.1 ng/mL for the patients evaluated. The estimated effect-site concentrations of remifentanil associated with a 50% and 95% probability of reaching MOAA/S score of 3 were 1.28 and 2.51 ng/mL, respectively. Conclusion: Plate removal of maxilla can be successfully performed without any pain or adverse effects by using the optimal remifentanil effect-site concentration ($Ce_{50}$, 1.28 ng/mL; $Ce_{95}$, 2.51 ng/mL) combined with sedation using dexmedetomidine.

• 한국임상약학회지
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• 제22권3호
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• pp.202-210
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• 2012

Methoxy polyethylene glycol-epoetin beta (MPG-EPO), a continuous erythropoietin receptor activator, is a new erythropoiesis-stimulating agent with a long half-life. The purpose of this prospective study is to assess the effects of once-monthly subcutaneous MPG-EPO on hematological responses and nutritional status in peritoneal dialysis patients. Forty four patients undergoing stable peritoneal dialysis were enrolled into the study. Darbepoetin alfa therapy, in peritoneal dialysis patients, was converted to the monthly administration of subcutaneous MPG-EPO for 6 months. The starting dose of MPG-EPO was based on the previous weekly dose of darbepoetin alfa. The dose adjustments were performed to maintain the hemoglobin (Hb) levels in a target range of 10.5-11.0 g/dL. If the Hb levels exceeded 11.0 g/dL, MPG-EPO was temporarily interrupted for 1 month. The mean Hb levels were stable with the values of $9.5{\pm}1.1$ g/dL at baseline, and $10.4{\pm}0.9$ g/dL at the 6th month after conversion. The mean differences in the changes of Hb levels between the baseline and the 6th month were $0.9{\pm}1.4$ g/dL, which was statistically significant. However, the mean differences of iron, transferrin saturation and ferritin concentrations were not significant. It did not show significant differences in the changes of the nutritional parameters. These results suggest that the once-monthly subcutaneous administration of MPG-EPO for 6 months effectively maintains the Hb levels and nutritional status in peritoneal dialysis patients. Taken together, the once-monthly subcutaneous administration of MPG-EPO was practical and might improve the clinical compliance for the management of renal anemia in peritoneal dialysis patients.

• Biomolecules & Therapeutics
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• 제4권1호
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• pp.78-83
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• 1996

The pharmacokinetics and tissue distribution of DA-3285 (recombinant human erythropoietin, recently manufactured by Research Laboratories of Dong-A Pharmaceutical Company) were studied in the laboratory animals. The plasma, urine, and tissue concentration of DA-3285 were measured by a double-antibody sandwich enzyme immunoassay. After intravenous administration of DA-3285, 20, 100, 500 and 2500 units/kg to rats, the plasma concentrations declined polyexponentially with the terminal half-lives of 2.15, 2.10, 2.31, and 2.35 hr, respectively. Total body clearance (20.7∼26.6 mι/hr/kg) and apparent volume of distribution at steady state (57.2∼70.1 mι/kg) were independent of the dose and AUC increased proportionally with the dose. The renal clearance was much lower than total body clearance, suggesting that extrarenal clearance, presumably metabolism , plays a significant role in elimination of DA-3285. In all rat tissues, the tissue to plasma ratios were smaller than unity, indicating less affinity of DA-3285 to rat tissues and was proved by considerably less value of Vdss. After 3 times a week for consecutive 3 weeks i.v. administration of DA-3285, 100 units/kg to rats, the plasma concentrations and pharmacokinetic parameters of DA-3285 were not significantly different from those in a single administration. After s.c. administration to the rat, plasma concentrations of DA-3285 peaked at 6 hr and the extent of bioavailability was 26.7%. In mice, rabbits and dogs, at DA-3285 dose of 100 units/kg, the mean terminal haw-lives were 2.78, 3.05, and 4.01 hr, respectively. Compared with reported data in the literatures, DA-3285 has similar properties to rh-EPO manufactured by other companies in view of pharmacokinetics.