• 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.

• The Korean Journal of Food And Nutrition
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• v.23 no.2
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• pp.141-146
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• 2010

Cisplatin(cis-diamminedichloroplatium) is one of the most effective anti-cancer drugs being clinically used in the treatment of solid tumors. Despite its therapeutic benefits, its use in clinical practice is often limited because of dose related toxicity. It is known that yeast cell wall beta-glucans possess immuno-modulating properties, which allows for their application in antitumor therapy. IS2 is a kind of beta-glucan derived from the cell wall of mutated Saccharomyces cerevisiae, which exhibits anti-cancer activity in vitro and in vivo. The present study explored the possibility of combination therapy of IS2 with cisplatin. In experimental metastasis of colon26-M3.1 cells, prophylactic intravenous administration of IS-2 in combination with cisplatin effectively inhibited tumor metastasis compared with cisplatin alone or IS-2 treatment in vivo. IS-2 effectively enhanced Th1 type cytokines including IFN-$\gamma$, IL-2, IL-12 and GM-CSF. Simultaneously, this combined treatment inhibited production of Th2 type cytokines compared with control. These results suggested that IS-2 can be applied in combination therapy with anti-cancer drugs to minimize their side effects.

• Archives of Pharmacal Research
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• v.18 no.4
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• pp.219-223
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• 1995

Rectal absorption of opeprazole, a proton pump inhibitor, from suppositories was studied in rabbits. The suppositories were prepared by the conventional melting method with two types of bases, water-soluble polyethylene glycol (PEG) 4000 and oil-soluble Witepsol H15 bases, and administered intractally (ir) to rabbits at a dose of 10 mg omeprazole/kg. The plasma omeprazole concentration-time profiles of the two suppositories were compared with those following intravenous 9iv) administration of the same dose. There were no significant differences between the two suppositories in bioabailabilities and peak plasma concentrations $(C_{max})$. Bioavaiabilities and $C_{max}$ of PEG- and Witpsol suppositories were 30.3 and 33.9%, and 7.0 and $5.6\mug/ml$, resepectively. However, PEG suppository showed significantly (p<0.05) shorter time to reach peak plasma concentration $(T_{max})$ mean absorption time (MAT) and mean residence time in the plasma (MRT) than Witepsol suppository. The $T_{max}$ MRT nad MAT were 25.0, 83.0 and 38.5 min for PEG syppository, but were 90.0, 122.5 and 78.0 min for Wiepsol supposiotory, respectively. These differences between thw two suppositories could be explanined by the difference in the in vitro dissolution rates between the suppositories. The dissolution of omeprazole form PEG suppository was reportedly much faster than that from Witepsol suppository. It suggests that plasma profiles of omeprazole, especially $C_{max}$ MAT and MRT, could be controlled by modifying the in vitro dissolution rate of the drug from the suppositories. Above results suggest that rectal suppository is worth developing as an alternative dosage form of omeprazole to the conventional oral preparations which need sophisticated treatments, such as enterix coating, to prevent acid degradation of the drug in the stomach fluid.

• The Korean Journal of Pain
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• v.27 no.3
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• pp.219-228
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• 2014

Background: A lipo-prostaglandin E1 agonist is effective for the treatment of neurological symptoms of spinal stenosis when administered by an oral or intravenous route. we would like to reveal the therapeutic effect of an epidural injection of lipo-prostaglandin E1 on hyperalgesia in foraminal stenosis. Methods: A total of 40 male Sprague-Dawley rats were included. A small stainless steel rod was inserted into the L5/L6 intervertebral foramen to produce intervertebral foraminal stenosis and chronic compression of the dorsal root ganglia (DRG). The rats were divided into three groups: epidural PGE1 (EP) (n = 15), saline (n = 15), and control (n = 10). In the EP group, $0.15{\mu}g{\cdot}kg-1$ of a lipo-PGE1 agonist was injected daily via an epidural catheter for 10 days from postoperative day 3. In the saline group, saline was injected. Behavioral tests for mechanical hyperalgesia were performed for 3 weeks. Then, the target DRG was analyzed for the degree of chromatolysis, chronic inflammation, and fibrosis in light microscopic images. Results: From the fifth day after lipo-PGE1 agonist injection, the EP group showed significant recovery from mechanical hyperalgesia, which was maintained for 3 weeks (P < 0.05). Microscopic analysis showed much less chromatolysis in the EP group than in the saline or control groups. Conclusions: An epidurally administered lipo-PGE1 agonist relieved neuropathic pain, such as mechanical hyperalgesia, in a rat foraminal stenosis model, with decreasing chromatolysis in target DRG. We suggest that epidurally administered lipo-PGE1 may be a useful therapeutic candidate for patients with spinal stenosis.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.4
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• pp.321-326
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• 2014

Testicular torsion results with the damage of the testis and it is a surgical emergency. Pyrrolidine dithiocarbamate (PDTC) is a low-molecular-weight antioxidant and potent inhibitor of nuclear factor kappa B (NF-${\kappa}B$) activation. In this study, we aimed to investigate the effects of PDTC to testicular torsion-detorsion (T/D) injury. Forty adult male Sprague-Dawley rats were separated into four groups. A sham operation was performed in group I. In group II, torsion is performed 2 hours by 720 degree extravaginally testis. In group III, 4 h reperfusion of the testis was performed after 2 h of testicular torsion. In group IV, after performing the same surgical procedures as in group III, PDTC (100 mg/kg, intravenous's) was administered before 30 min of detorsion. The testes tissue malondialdehyde (MDA), superoxide dismutase (SOD) catalase (CAT) level was evaluated. Histological evaluations were performed after hematoxylin and eosin staining. Testicular tissue MDA levels were the highest in the T/D groups compared with treatment group. Administration of PDTC prevented a further increase in MDA levels. Significant decrease occurred in CAT and SOD levels in treatment group compared with the control group. The rats in the treatment group had normal testicular architecture. The results suggest that PDTC can be a potential protective agent for preventing the biochemical and histological changes related to oxidative stress in testicular injury caused by testis torsion.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.3
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• pp.245-251
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• 2013

The purpose of this study was to investigate the effects of fluvastatin on the pharmacokinetics of repaglinide in rats. The effect of fluvastatin on P-glycoprotein and CYP3A4 activity was evaluated. The pharmacokinetic parameters and blood glucose concentrations were also determined after oral and intravenous administration of repaglinide to rats in the presence and absence of fluvastatin. Fluvastatin inhibited CYP3A4 activity in a concentration-dependent manner with a 50% inhibition concentration($IC_{50}$) of 4.1 ${\mu}M$ and P-gp activity. Compared to the oral control group, fluvastatin significantly increased the AUC and the peak plasma level of repaglinide by 45.9% and 22.7%, respectively. Fluvastatin significantly decreased the total body clearance (TBC) of repaglinide compared to the control. Fluvastatin also significantly increased the absolute bioavailability (BA) of repaglinide by 46.1% compared to the control group. Moreover, the relative BA of repaglinide was 1.14- to 1.46-fold greater than that of the control. Compared to the i.v. control, fluvastatin significantly increased the $AUC_{0-{\infty}}$ of i.v. administered repaglinide. The blood glucose concentrations showed significant differences compared to the oral controls. Fluvastatin enhanced the oral BA of repaglinide, which may be mainly attributable to the inhibition of the CYP3A4-mediated metabolism of repaglinide in the small intestine and/or liver, to the inhibition of the P-gp efflux transporter in the small intestine and/or to the reduction of TBC of repaglinide by fluvastatin. The study has raised the awareness of potential interactions during concomitant use of repaglinide with fluvastatin. Therefore, the concurrent use of repaglinide and fluvastatin may require close monitoring for potential drug interactions.

• Microbiology and Biotechnology Letters
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• v.3 no.2
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• pp.69-72
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• 1975

Isolation of the toxic substance which was produced by Streptentyces sp. and it's biorhemical characterestics and toxicity to fishes were reported in the previous paper. The present report includes antibiotic activity of the substance, inhibitory activity of the substance on the succinic dehydrogenase of fishes, and its effect on the blood corpuscles of a rabbit. An evident antibiotic activity of this substance was observed on Candida yeasts, but n$ot^1$on molds or bacteria. The substance inhibited the growth of Candida japonica and C. utilis to the 50％ at the concentrations of 7.5 and 10.2ug per ml, respectively. The activity of succinic dehydrogenase obtained from various organs of Cyprinous carpio L. was also found to be inhibited by this substance. Original activities of the enzymes from tht brain, kidney, and liver, were inhibited by 75.4％, 38.2％, and 26.2％, respectively, but not the enzymes from the heart and spleen. Neither leukopenia nor leukocytosis was detected after the intravenous administration of the substince to the rabbit at the level of 6 mg per 2 kg body weight.

• Archives of Pharmacal Research
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• v.19 no.5
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• pp.359-367
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• 1996

The pharmacokinetics of LB20304 was investigated following intravenous (IV) and oral administration to rats and dogs. Additionally, in vitro metabolism and serum protein binding studies were also conducted. The total body clearance, apparent volume of distribution, terminal half-life, and extent of bioavailability were 21.8 ml/min/kg, 2265 ml/kg, 93.6 min, and 30.8% for rats; and 7.95 ml/min/kg, 4144 ml/kg, 363 min, and 81.1% for dogs, respectively. LB20304 was stable in the liver microsome containing NADPH generating system and its serum protein binding was 58.5-65.8% for rats, 19.1-29.6% for dogs, and 56.9-59.6% for humans. Its tissue concentration levels in lever, stomach, small intestine, and kidney were 9.5 to 26.1 times greater than plasma level, but the concentration in testis was quite low and that in brain was negligible in rats. The 48 hr urinary recovery of the dose was 44% for IV dosing and 14% for oral dosing, shereas the 48 hr biliary recovery of the dose was 6.4% for IV dosing and 4.5% for oral dosing in rats. In summary, the pharmacokinetic properties of LB20304 were characterized by its good oral absorption, long plasma half-life, and good tissue distribution.

• Korean Journal of Clinical Pharmacy
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• v.8 no.2
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• pp.89-94
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• 1998

Seasonal rhythmic changes in gentamicin pharmacokinetics was evaluated in 10 healthy male volunteers after single intravenous 80 mg administration of gentamicin at 9:00 a.m. during summer and winter. The mean terminal half-life and AUC of gentamicin were $3.56\pm0.14\;hr\;and\;25.03\pm2.84\;{\mu}g/ml{\cdot}hr$ in winter and $3.08\pm0.41\;hr\;and\;21.84\pm2.51\;{\mu}g/ml{\cdot}hr$ in summer. The mean total body clearance $(CL_t)$ and elimination rate constant $(k_{10})$ of gentamicin was $3.17\pm0.43\;L/hr,\;0.458\pm0.06\;hr^{-1}\;in\;winter\;and\;3.66\pm0.45\;L/hr,\;0.561\pm0.07\;hr^{-1}$ in summer, The mean volumn of distribution $(V_{dss})$ of gentamicin at steady state was $12.65\pm1.09$L in winter and $12.39\pm1.25$ L in summer. Serum concentrations of gentamicin in winter were increased significantly during 4-8 hr (p<0.05) compared to those of gentamicin in summer. The elimination rate constant $(k_{10})$ of gentamicin in winter was decreased significantly $(p<0.05)$ compared to that of gentamicin in summer. The mean volume of distribution at steady state $(V_{dss})$, AUC, mean total body clearance ($CL_t$) and terminal half-life of gentamicin in the winter were increased but were not significant. The mean intrasubject fluctuations in terminal half-life, AUC and $CL_t$ between winter and summer were 8.2, 11.0 and $6.0\%$ respectively.

• Journal of the korean academy of Pediatric Dentistry
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• v.24 no.4
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• pp.823-829
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• 1997

The patients visiting pediatric dental office have been being younger than the previous, and they were often combined with systemic disease. But, we aren't able to perform the verbal communication, because of their impediment and youthfullness. And, we can't carry out the behavior control via physical restraint, as the developed social structure and the attitude of children and their parents. So, the importance and concerning of conscious sedation using sedative medicine are increased by time and time. Among the various conscious sedation, Chloral Hydrate and Nitrous Oxide inhalation are most popularly used, and barbiturates, benzodiazepine, opioids and hydroxyzine are used often. But, these medications have some side-effects and adverse reactions, may be failed to sedate the children. And limited use of medically compromised patients, especially for ASA class III, IV or more dangerous patients. We, the Department of Pediatric Dentistry, Chosun University have met some dangerous situation due to unfavorable pharmacogenic reactions, but we can control the situation and get well healed results. The below results are common situations and their solutions during conscious sedation. 1. By the intravenous administration, thrombophlebitis is the most common side-effects, but it may be healed with time without any special treatment. 2. Under the definitive guidelines about conscious-sedation, we can perform a safe conscious sedation for ASA class III patients. 3. When adversed reaction of Benzodiazepine is occured, it could be cared effectively with benzodiazepine antagonist, named Flumazenil.