• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.108-108
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• 1995

Pharmacokinetic studies on time-course of blood levels, tissue distribution, and excretion of G009, a potential hepatoprotective agent, were performed in male rats after a single oral dose(20mg/kg) of $\^$14/C-labelled G009. The radioactivity concentrations in plasma during 0～3 hours are low, but subsequently increase to a maximum at 12 hours after dosing. $\^$14/C-G009 was well distributed to all tissue. Tissue concentration profiles of radioactivity vary among tissues on time-course after administration. G009(single oral dosage) was distributed and/or absorbed at gastric intestines and excretional organs for initial time of 0-7 hours, and distributed to most tissue at 12-24 hours. In special, the concentration of radioactivity in tiller at 48 hours were 1% of total radioactivity of $\^$14/C-G009 administered. The expired air, urinary and fecal excretion of radioactivity within 24hours after administration were 61.5%, 1.9% and 21.2% of total radioactivity of $\^$14/C-G009 administered. The biliary excretion of radioactivity in rat increased slightly for 0-6 hours after administration. The biliary excretion of radioactivity within 48hours were 1.97%.

• Journal of Pharmaceutical Investigation
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• v.24 no.2
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• pp.73-83
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• 1994

Applications of liposomes as a drug carrier for the oral delivery of poorly-absorbable macromolecular drugs have been limited, because of their instability in gastrointestinal environments including pH, bile salts, and digestive enzymes. Two polysaccharides, dextran(DX) and pullulan(PL), were introduced to the preformed liposomes in order to enhance the stability. Palmitoyl derivatives of polysaccharides, palmitoyldextran(PalDX) and palmitoylpullulan(PalPL), were synthesizd and introduced to the liposomes during preparation for the same purpose of stability. The effects of these polysaccharides coating were evaluated basically by physical properties of particle size distribution and optical microscopy, then compared with uncoated liposomes by the observations of both in vitro stability and in vovo absorption characteristics. The geometric mean diameters of polysaccharide-coated liposomes were greater than that of uncoated liposome, showing the outermost polysaccharide-coated layer under the optical microscopy. In vitro stabilities of uncoated or polysaccharides-coated liposomes were measured by turbidity changes in various pH buffer solutions containing sodium choleate as bile salts. While uncoated liposome was very sensitive to bile salts, polysaccharides-coated liposomes were stable in relatively higher concentrations of sodium choleate, giving the results of better stability of PalDX- and PalPL-coated liposomes than that of DX- and PL-coated liposomes. After liposomal encapsulation of acyclovir(ACV), an antiviral agent as a model drug, it has been administered orally to rats as dose of ACV 40 mg/kg. Plasma concentrations of ACV were assayed by HPLC and analyzed by model-independent pharmacokinetics. Pharmacokinetic parameters of Cmax, tmax, and [AUC] have been compared.

• Journal of Pharmaceutical Investigation
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• v.39 no.5
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• pp.359-366
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• 2009

In this study, paclitaxel-loaded lipid nanosuspension (PxLN) was prepared and the in vivo profiles after intravenous administration in rats were investigated. We compared the manufacturing processes depending on the temperature: PxLN-H for a hot homogenization process and PxLN-C for solidification of lipid-drug mixtures by liquid nitrogen. Both formulations showed submicron size distribution and the similar drug loading efficiency of about 70%. In vitro release of PxLNs and Taxol$^{(R)}$ performed by a dialysis diffusion method showed similar pattern for PxLN-H and Taxol$^{(R)}$, but the reduced release profile for PxLN-C. PxLN or Taxol$^{(R)}$ was intravenously administered to the rats at a dose of 5 mg/kg as paclitaxel. The drug in blood samples were assayed by the HPLC/MS/MS method. The AUC$_t$ of PxLN-H was 3.4-fold greater than that of Taxol$^{(R)}$. PxLN-H gave higher biodistribution in all tissues than did Taxol$^{(R)}$. In addition, it maintained the higher drug concentration for 12 h. This lipid nanosuspension might be a promising candidate for an alternative formulation for the parenteral delivery of poorly water-soluble paclitaxel.

• Applied Microscopy
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• v.18 no.1
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• pp.60-76
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• 1988

Chick embryos which have received a single injection of the organophosphate compound, malathion (0.1 mg/0.05 ml, 0.5 mg/0.05 ml, 1.0 mg/0.05 ml or 2.0 mg/0.05 ml) via the yolk sac at certain times (2 days, 4 days or 6 days after incubation) have been investigated. After 9 days of incubation, chick embryos were harvested to examine the effects of malathion on the ultrastructure and the acetylcholinesterase(AChE) activity of the developing spinal cord. The effects of simultaneous injection of malathion and nicotinamide were also compared. On ultrastructural findings, neurons in the ventral horn of spinal cord showed to be inhibited in their differentiation by malathion; nuclear irregularity, separation of nuclear membranes, reduction of ribosomal distribution, and cytoplasmic vacuoles were observed. In the younger embryos treated with relatively high doses of malathion, nucleus and cytoplasmic organelles of neurons were severely destroyed, and the neurons were shown to be necrotic. On cytochemical study of AChE by electron microscope, the positive reaction products of AChE were localized at the membranes of nucleus and endoplasmic reticulum of neurons. Inhibition of AChE activity was severe in groups treated with relatively low doses of malathion. Nicotinamide (5.0 mg/0.05 ml) alleviated malathion-induced morphological alterations. In conclusion, it is suggested that malathion changes the ultrastructure and reduces. AChE activity in differentiating neurons, and the severity of which is consistently dose- and age-dependent.

• Archives of Pharmacal Research
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• v.17 no.2
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• pp.124-130
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• 1994

Plasma phamacokinetics and renal excretion of theophylline (TP) and its metabolities were ivnestigated in rats. Plasma concentrations of TP declined in a monoexponential manner, while those of 1-methyluric (MU) and 1,3-dimethyluric(DMU) declined in a biexponential manner upon respective iv bolus injection of each compound at 6mg/kg dose. The total body clearances $(CL_r)$ of the metabolites were 4-6 fold larger than that of TP, while the distribution volumes of them at steady-state $(Vd_{ss})$ were 40-50% smaller than that of TP. The metabolites showed their plasma peaks in 30 min after iv injection of TP indicating than that to MU. Renal excretion of TP and its metabolites was studied in urine flow rate (UFR)-controlled rats. The renal clearance $(CL_r)$ of TP was inversely related to pasma TP concentrations, and much smaller than the glomerular filtration rate (GFR) suggesting tubular secretion and profound reabsorption in the renal tubule. The $(CL_r)$ of each metabolite also showed that inverse relationship, but far exceeded GFR suggesting that tubular secretion than GFR by ip injection of probenecid (142.7 mg/kg). It supports that the metabolies are secreted in the renal tubule, and suggests that they share a common transport system in their sectrtion processes with probenecid. On the other hand, the $(CL_r)$ of TP was not affected significantly by the probenecid treatment. Considering the inverse relationship of TP between the $(CL_r)$ and its ploasma concentrations,no effect of probenecid on $(CL_r)$ of TP is most likely due to negligible contribution of the secretion to the overall $(CL_r)$ of TP.

• Journal of Ginseng Research
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• v.38 no.4
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• pp.233-238
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• 2014

Background: The actin cytoskeleton in podocytes is essential for the maintenance of its normal structure and function. Its disruption is a feature of podocyte foot-process effacement and is associated with proteinuria. ${\alpha}$-Actinin-4 in podocytes serves as a linker protein binding the actin filaments of the cytoskeleton. Methods: To investigate the effect of ginseng total saponin (GTS) on the pathological changes of podocyte ${\alpha}$-actinin-4 induced by diabetic conditions, we cultured mouse podocytes under normal glucose (5mM) or high glucose (HG, 30mM) conditions, with or without the addition of advanced glycosylation end products (AGE), and treated with GTS. Results: In confocal imaging, ${\alpha}$-actinin-4 colocalized with the ends of F-actin fibers in cytoplasm, but diabetic conditions disrupted F-actin fibers and concentrated ${\alpha}$-actinin-4 molecules at the peripheral cytoplasm. GTS upregulated ${\alpha}$-actinin protein in a time- and dose-dependent manner, and suppressed the receptor for AGE levels in western blotting. Diabetic conditions, including HG, AGE, and both together, decreased cellular ${\alpha}$-actinin-4 protein levels at 24 h and 48 h. Such quantitative and qualitative changes of ${\alpha}$-actinin-4 protein induced by diabetic conditions were mitigated by GTS. Conclusion: These findings imply that both HG and AGE have an influence on the distribution and amount of ${\alpha}$-actinin-4 in podocytes that can be recovered by GTS.

• Radiation Oncology Journal
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• v.36 no.4
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• pp.276-284
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• 2018

Purpose: Traditionally, three-dimensional conformal radiation therapy (3D-CRT) is used for neoadjuvant chemoradiation in locally advanced rectal cancer. Intensity-modulated radiation therapy (IMRT) was later developed for more conformal dose distribution, with the potential for reduced toxicity across many disease sites. We sought to use the National Cancer Database (NCDB) to examine trends and predictors for IMRT use in rectal cancer. Materials and Methods: We queried the NCDB from 2004 to 2015 for patients with rectal adenocarcinoma treated with neoadjuvant concurrent chemoradiation to standard doses followed by surgical resection. Odds ratios were used to determine predictors of IMRT use. Univariable and multivariable Cox regressions were used to determine potential predictors of overall survival (OS). Propensity matching was used to account for any indication bias. Results: Among 21,490 eligible patients, 3,131 were treated with IMRT. IMRT use increased from 1% in 2004 to 22% in 2014. Predictors for IMRT use included increased N stage, higher comorbidity score, more recent year, treatment at an academic facility, increased income, and higher educational level. On propensity-adjusted, multivariable analysis, male gender, increased distance to facility, higher comorbidity score, IMRT technique, government insurance, African-American race, and non-metro location were predictive of worse OS. Of note, the complete response rate at time of surgery was 28% with non-IMRT and 21% with IMRT. Conclusion: IMRT use has steadily increased in the treatment of rectal cancer, but still remains only a fraction of overall treatment technique, more often reserved for higher disease burden.

• Radiation Oncology Journal
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• v.12 no.3
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• pp.331-336
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• 1994

Purpose : To assess the effectiveness and problems of the primary radiation therapy and salvage surgery in a series of patients affected by T1-T2NO glottic cancers treated from 1985 to 1991 at the Pusan National University Hospital. Materials and Methods : From 8/85 to 12/91,34 patients affected by early glottic carcinoma histologically proven were treated with curative radiation therapy, Distribution of patients according to T stage was 30 for T1 and 4 for T2. Male to female ratio was 33:1. Age of patients ranged from 31 to 73 with mean age of 58 years. All of the patients were treated with radical radiation with total tumor dose of 63-75. 3Gy(median 68.2Gy), of 5 weekly fractions of 1.8-2Gy and with 6MV photon beams through two laterally opposed fields. Results : The overall 5-year local control rates were $74\%$(8/30) for Tl, and $25\%$(3/4) for T2. The main cause of failure was progression or recurrence in T(10/11). One failures were observed in T and N at the same time. Of these 11 patients, 9($81\%$) were salvaged with surgery, After surgical salvage of radiation failures, the 5-year survival rates were $96\%$ for T1 and $75\%$ for T2. Among the survivors, $73\%$ of T1 and $33\%$ of T2 were able to preserve the larynx. Conclusion : It can be concluded that radiotherapy is the first choice in the treatment of glottic T1 carcinoma.

• Journal of Pharmaceutical Investigation
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• v.36 no.5
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• pp.299-304
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• 2006

The aim of this study was to investigate the effect of deformable liposomes with sodium cholate on the skin permeation and skin deposition of arbutin, a hydrophilic skin-whitening agent. Various compositions of liposomes were prepared by the extrusion method. Particle size distribution and entrapment efficiency were determined by the laser light scattering and the gel permeation chromatography, respectively. The in vitro rat skin permeation and deposition of arbutin in various skin layers were investigated using the Keshary-Chien diffusion cells at $37^{\circ}C$. The average particle size of the deformable liposomes ranged from 217.4 to 117.4 nm, depending on the composition. The entrapment efficiency was dependent on surfactant concentration and loading dose of arbutin. The permeation rate of 5% arbutin in deformable liposomes was $8.91({\pm}1.33){\mu}g/cm^2/h$, and was not significantly different from 5% arbutin aqueous solution $[9.82({\m}0.86){\mu}g/cm^2/h]$. The deposition of arbutin was $43.34({\pm}12.13)$ and $16.99({\pm}7.83){\mu}g/cm^2$ in stratum corneum layer and epidermis/dermis layer, respectively, after 12 h of permeation study. These results are consistent with several earlier studies for the localization effect of liposomal formulations in stratum corneum, and demonstrated the feasibility of the deformable liposomes as a promising carrier for the skin deposition of hydrophilic skin-whitening compounds.

• Journal of Pharmaceutical Investigation
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• v.30 no.3
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• pp.159-166
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• 2000

Kunitz-type soybean trypsin inhibitor (SBTI) and chondroitin sulfate (A, and C type) were conjugated using sodium periodate method. And the physicochemical, pharmacokinetic properties and immunogenecity of the conjugates (Chon-A-SBTI or Chon-C-SBTI) were characterized. We expected the conjugation using chondroitin sulfate to reduce the immunogenecity and to improve the pharmacological effect. As the results, the mean molecular weight of the conjugate highly increased. After I.V. injection of the radiolabeled conjugates or native SBTI into mice, it was found that native SBTI showed rapid elimination from plasma, whereas Chon-A-SBTI and Chon-C-SBTI were slowly eliminated. Organ distribution of the two agents at 30 min after I.V. injection was different : Chon-A-SBTI or Chon-C-SBTI accumulated to a large extent in the liver (13% in Chon-A-SBTI and 16% in Chon-C-SBTI), whereas native SBTI was taken up more rapidly by the kidney (107% dose/g of tissue) and excreated into the urine (26%). In addition we evaluated the therapeutic value of the conjugates by using the sublethal septic shock model caused by pseudomonal elastase and tested the immunogenecity by passive cutaneous anaphylaxis shock (PCA). The conjugates were more effective than native SBTI against pseudomonal elastase induced septic shock in guinea pig. In case of the conjugates, the pharmacological and therapeutic effect lasted over 3 hours long. In immunogenecity test, both of the conjugates showed the reduction of their immunogenecity, especially Chon-A-SBTI looked most effective.