• Asian Pacific Journal of Cancer Prevention
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• 제16권18호
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• pp.8419-8423
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• 2016

Purpose: Anti-cancer activity evaluation of aqueous extract of CRUEL (herbomineral formulation) capsules on renal cell carcinoma cell lines, and exploration of mechanisms of cell death. Materials and Methods: To detect the cytotoxic dose concentration in renal cell carcinoma (RCC) cells, MTT assays were performed and morphological changes after treatment were observed by inverted microscopy. Drug effects against RCC cell lines were assessed with reference to cell cycle distribution (flow cytometry), anti-metastatic potential (wound healing assay) and autophagy(RT-PCR). Results: CRUEL showed anti-proliferative effects against RCC tumor cell lines with an IC50 value of ${\approx}4mg/mL$ in vitro., while inducing cell cycle arrest at S-phase of cell cycle and inhibiting wound healing. LC3 was found to be up-regulated after drug treatment in RT-PCR resulting in an autophagy mode of cell death. Conclusions: This study provides the experimental validation for antitumor activity of CRUEL.

• 농촌의학ㆍ지역보건
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• 제9권1호
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• pp.109-116
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• 1984

The epidemiological information on 156 cases of acute drug intoxication treated at emergency room of Sin An Dai-Woo Hospital in Bi-Gum island during the year of 1981-1982 were reviewed and analyzed. And the findings obtained was as follows : 1) Annual incidence rate of acute drug intoxication was 3.3 per 1,000 in habitants (male 3.5, female 3.1). 2) In both sexes the highest incidence was obsesved in the age group of 20~49 years with 7.6 in male and 6.2 in female per 1,000 inhabitants. 3) In both sexes the highest ease distribution was observed during summer season of July and August (male 33.2%, female 26.4%). 4) Eating pesticides was the most frequently used for suicide purpose in both sexes (male 89. 3%, female 82.2%). 5) In terms of foundation for conclusion to eating poison, "by guardion's explanation" was the highest rate in both groups of eating pesticides (97.8%) and eating rodentcides(77.8%). 6) The case fatality rate due to eating poison was 4.5% (male 5.9%, female 2.8%). 7) In haspitalization days, the most cases was observed at less than 3 days (male 73.8%, female 79.2%).

• 약학회지
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• 제44권3호
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• pp.245-250
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• 2000

Because nonsteroidal anti-inflammatory drugs are reported to cause fluid retention and hypertension by inhibition of prostaglandin synthesis, the effects of piroxicam on pharmacodynamics and pharmacokinetics of nifedipine were studied in male spontaneously hypertensive rats. They received nifedipine (0.5 mg/kg) alone or combined with piroxicam (5 mg/kg) intravenously. Plasma levels norepinephrine, an index of sympathetic stimulation, were measured prior to each treatment and 5 min after drug administration. Changes in blood pressure were examined serially and blood samples for analysis of nifedipine were also taken for 6 hr following drug administration. Plasma nifedipine concentration were assayed by HPLC and pharmacokinetic parameters were calculated. Blood pressure was reduced (p<0.01), but plasma norepinephrine level was increased (p<0.05) by nifedipine administration. Anti-hypertensive effect of nifedipine was potentiated (p<0.05) by piroxicam coadministration, but effect of nifedipine on plasma norepinephrine level was not affected. In case of rats received nifedipine and piroxicam, plasma nifedipine concentrations were higher (p<0.05) than those from rats received nifedipine alone at 2,3,4,5 and 6 hours following drug administration. The area under the plasma concentration vs. time curve was increased (p<0.05), while the elimination rate constant was decreased (p<0.01) by piroxicam coadministration. No significant differences were observed in the plasma clearance, apparent volume of distribution and elimination half-life. Thus, piroxicam not only potentiated antihypertensive effect of nifedipine, but also altered nifedipine pharmacokinetics in the rats. It is concluded that the potentiation of nifedipine antihypertensive effect might correlate with the increment of its plasma concentration by piroxicam coadministration.

• Journal of Pharmaceutical Investigation
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• 제36권4호
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• pp.263-269
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• 2006

Deficiencies in the early ADMET(absorption, distribution, metabolism, elimination and toxicity) information on drug candidate extract a significant economic penalty on pharmaceutical firms. Microscale cell culture analogue-microscale gastrointestinal(${\mu}CCA-{\mu}GI$) device using Caco 2, L2 and HEp G2/C3A cells, which mimic metabolic process after absorption occurring in humans was used to investigate the toxicity of the model chemical, acetaminophen(AAP). The toxicity of acetaminophen determined after induction of CYP 1A1/2 in Caco 2 cells was not significant. In a coculture system, although no significant reduction in viability of HEp G2/C3A and L2 cells was found, approximately 5 fold increase in the CYP 1A1/2 activity was observed. These results appear to be related to organ-organ interaction. The oral administration of a drug requires addition of the absorption process through small intestine to the current ${\mu}CCA$ device. Therefore, a perfusion coculture system was employed for the evaluation of the absolution across the small intestine and resulting toxicity in the liver and lung. This system give comprehensive and physiologic information on oral uptake and resulting toxicity as in the body. The current ${\mu}CCA$ device can be used to demonstrate the toxic effect due to organ to organ interaction after oral administration,

• 보건행정학회지
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• 제21권1호
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• pp.132-157
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• 2011

The purpose of this article is to examine the cause of policy non-compliance in the case of pharmaceutical rebates from the perspective of rational choice institutionalism. In Korea, there have been rebates practices between pharmaceutical companies and hospitals since the introduction of the Actual Remuneration System for insured medicine in 1999. The government has chosen the policy means of punishment to eliminate pharmaceutical rebates but the illegal practices are still widespread. Institution in rational choice institutionalism usually reflects the incentives and preferences of actors, and the Actual Remuneration System has resulted in a the lack of procedures to ensure savings on drug expenditures. Pharmaceutical rebates are the product of the institutions which reflect their incentives: the Actual Remuneration System, the current pricing policy for generic drugs, the drug distribution system, and so on. In the end, the problem of the rebates is the consequence of policy non-compliance as actors' rational choice because their incentives lead to opportunistic behaviors. We should therefore understand the incentive structure of policy stakeholders, which is derived from the view of new institutionalism; also, the newly designed Korean drug pricing policy reform must be compatible with the incentive structure.

• Archives of Pharmacal Research
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• 제28권3호
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• pp.370-375
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• 2005

The objective of this study was to develop a new reverse micelle-based microencapsulation technique to load tetracycline hydrochloride into PLGA microspheres. To do so, a reverse micellar system was formulated to dissolve tetracycline hydrochloride and water in ethyl formate with the aid of cetyltrimethylammonium bromide. The resultant micellar solution was used to dissolve 0.3 to 0.75 g of PLGA, and microspheres were prepared following a modified solvent quenching technique. As a control experiment, the drug was encapsulated into PLGA microspheres via a conventional methylene chloride-based emulsion procedure. The micro­spheres were then characterized with regard to drug loading efficiency, their size distribution and morphology. The reverse micellar procedure led to the formation of free-flowing, spherical microspheres with the size mode of 88 ~m. When PLGA microspheres were prepared follow­ing the conventional methylene chloride-based procedure, most of tetracycline hydrochloride leached to the aqueous external phase: A maximal loading efficiency observed our experimental conditions was below $5\%$. Their surfaces had numerous pores, while their internal architecture was honey-combed. In sharp contrast, the new reverse micellar encapsulation technique permitted the attainment of a maximal loading efficiency of 63.19 $\pm$$0.64\%$. Also, the microspheres had smooth and pore-free surfaces, and hollow cavities were absent from their internal matrices. The results of this study demonstrated that PLGA microspheres could be successfully prepared following the new reverse micellar encapsulation technique.

• Archives of Pharmacal Research
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• 제26권12호
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• pp.1096-1101
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• 2003

To enhance the liver targeting and reduce the side effects of 5-fluorouracil (5-Fu), it was acylated by stearyl chloride to obtain .$\b{N}_{\b{1}}$stearyl-5-Fu (5-FuS). The chemical structure of the prodrug was confirmed by Nuclear Magnetic Resonance and Infrared Spectrometry. 5-FuS was incorporated into solid lipid nanoparticles (SLN), which were prepared by the physical agglomeration method. The mean diameter of 5-FuS-SLN was 240.19 nm and the drug loading was 20.53%. The release characteristics in vitro of 5-FuS-SLN were fitted to the first-order pharmacokinetic model. Compared with 5-Fu injection, a study on the distribution of 5-FuS-SLN in mice showed that 5-FuS-SLN could double 5-Fu concentration in mice livers. The main pharmacokinetic parameters of 5-FuS-SLN in rabbits is shown as follows: $V_d$=0.04336L/kg, $T_{1/2} \beta$=1.2834h, CL=0.1632 L/h. In conclusion, 5-FuS-SLN has significant liver targeting properties. The employment of a prodrug to enhance drug liposoluble properties and the preparation method presented in this paper, seem to be an alternative strategy to the traditional colloidal delivery system.

• Archives of Pharmacal Research
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• 제26권2호
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• pp.173-181
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• 2003

A polymeric micelle drug delivery system was developed to enhance the solubility of poorly-water soluble drug, biphenyl dimethyl dicarboxylate, DDB. The block copolymers consisting of poly(D,L-lactide) (PLA) as the hydrophobic segment and methoxy poly(ethylene glycol) (mPEG) as the hydrophilic segment were synthesized and characterized by NMR, DSC and MALDI-TOF mass spectroscopy. The size of the polymeric micelles measured by dynamic light scattering showed a narrow monodisperse size distribution with the average diameter less than 50 nm. The MW of mPEG-PLA, 3000 (MW of mPEG, 2 K; MW of PLA, 1K), and the presence of hydrophilic and hydrophobic segments on the polymeric micelles were confirmed by MALDI-TOF mass spectroscopy and NMR, respectively. Polymeric micelle solutions of DDB were prepared by three different methods, i.e. the matrix method, emulsion method and dialysis method. In the matrix method, DDB solubility was reached to 13.29 mg/mL. The mPEG-PLA 2K-1K micelle system was compared with the poloxamer 407 micelle system for their critical micelle concentration, micelle size, solubilizing capacity, stability in dilution and physical state. DDB loaded-polymeric micelles prepared by the matrix method showed a significantly increased aqueous solubility (＞5000 fold over intrinsic solubility) and were found to be superior to the poloxamer 407 micelles as a drug carrier.

• Archives of Pharmacal Research
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• 제18권3호
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• pp.141-145
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• 1995

Omeprazole, a proton pump inhibitor, was given intravenously (iv), orally (po), intraperitoneally (ip), hepatoportalvenously (pv), and intrarectally (ir) to rats at a dose of 72mg/kg in order to investigate the bioavailability of the drug, The extent of bioavailabilities of omeprazole administered through pv, ip, po, and ir routes were 88.5, 79.4, 40,8, and 38.7%, respectively. Pharmacokinetic analysis in this study and literatures (Regardh et al., 1985 : Watanabe et al., 1994) implied significant dose-dependency in hepatic first-pass metabolism, clearance and distribution, and acidic degradation in gastric fluid. The high bioavailability from the pv administration (88.5%) means that only 11.5% of dose was extracted by the first-pass metabolism through the liver at this dose (72 mg/kg). The low bioavailability from the oral administration (40.8%) in spite of minor hepatic first-pass extraction indicates low transport of the drug from GI lumen to portal vein. From the literature (Pilbrant and Cederberg, 1985), acidic degradation in gastric fluid was considered to be the major cause of the low transport. Thus, enteric coating of oral preparations would enhance the oral bioavailability substantially. The bioavailability of the drug from the rectal route, in which acidic degradation and hepatic first-pass metabolism may not occur, was low (38.7%) but comparable to that from the oral route (40.8 %) indicating poor transport across the rectal membrane. In this case, addition of an appropriate absorption enhancer would improve the bioavailability. Rectal route seems to be an possible alternative to the conventional oral route for omeprazole administration.

• Journal of Pharmaceutical Investigation
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• 제28권1호
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• pp.7-13
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• 1998

The captopril microcapsules were prepared and were investigated by measuring their size distribution using Scanning Electron Microscopy(SEM) and dissolution of captopril. Cetyl alcohol microcapsules prepared by emulsion melted-cooled method with various ratios of drug to cetyl alcohol were spherical and uniform. The release rate of cetyl alcohol microcapsules was decreased proportionally as the content of cetyl alcohol increased but, the particle size of microcapsules was increased. The surface of cetyl alcohol microcapsules was comparatively rough as drug content increased. Pellet type microcapsules were prepared using fluidized-bed coating system by spraying captopril solution on nonpareil-seeds followed by applying $Eudragit^{\circledR}$ RS solution containing propylene glycol as a plasticizer. The release rate of drug from pellet type microcapsules decreased as the content of $Eudragit^{\circledR}$ RS increased.