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Biomedical subjects

N S Kim

Publications and source records attributed to N S Kim.

At least 73 records · Page 4Linked to original sources
PubMed1994

Pharmacokinetics of RK-28 (a new radiosensitizer) and pharmaceutical design of a suppository form using rats.

The pharmacokinetics of RK-28, a new hypoxic cell radiosensitizer, was studied in rats following its intravenous, intraportal, oral, and rectal administration. The pharmaceutical design of an RK-28 suppository form was also examined. After intravenous injection, RK-28 was rapidly removed from the plasma (biological half-life of 17 min) and its area under the curve (AUC) was proportional to the amount of RK-28 administered. The absolute bioavailability of RK-28 was 59.7% for intraportal administration and 36.9% for oral administration. Following oral administration of RK-28, it seems likely that specific acid-catalyzed decomposition of RK-28 takes place in the stomach and then the absorbed RK-28 undergoes first-pass metabolism in the liver. When "solidified RK-28 suppository," made by solidifying molten RK-28, was inserted into the rectum, hepatic first-pass metabolism could be avoided substantially. The resulting absolute bioavailability of RK-28 increased to 75%. Furthermore, "RK-28 emulsion suppository," prepared by emulsifying RK-28 with 1-hexadecanol and hydrogenated castor oil (HCO 60) at 80 degrees C, showed a plasma concentration-time curve very suitable for radiation therapy; the maximum plasma concentration was attained 30 min after rectal administration and then decreased within a short period. Administration of "RK-28 emulsion suppository," resulted in an absolute bioavailability of 76%.

Administration, Oral↗
PubMed1994

Relationship between lipophilicity and skin permeability of various drugs from an ethanol/water/lauric acid system.

The in vitro skin permeability of 16 drugs with a wide range of lipophilicity (log P; -0.95-4.40) was evaluated by the use of an ethanol/water (60/40) binary vehicle with or without lauric acid as a permeation enhancer. The enhancing effect by the addition of lauric acid to the ethanol/water (60/40) binary vehicle could be observed from the aspect of both permeation rate and lag time. The permeation rate increased with an increase in the hydrophilicity of the drugs. It was considered that lauric acid exerts an effect on both the polar and nonpolar regions of lipids of the stratum corneum, and the cooperative interaction of ethanol and lauric acid increases the participation of the polar pathway of drugs. The relationship between lipophilicity and skin permeability of the drugs from the ethanol/water (60/40) binary vehicle with lauric acid showed a parabolic shape, with its peak at a more hydrophilic range (log P; 0.19) compared with other past references (log P; 2-3). The ethanol/water (60/40) binary vehicle with lauric acid appears to be a good candidate as a vehicle for transdermal therapeutic systems for hydrophilic drugs.

1-Octanol↗
PubMed1994

Preparation and evaluation of suppositories for RK-28 (a new radiosensitizer) using rabbits.

The pharmacokinetics of RK-28 [1-(4-hydroxy-2-butenoxy)methyl-2-nitroimidazole], a new hypoxic cell radiosensitizer, was studied following intravenous, oral, and rectal administration to rabbits. After an oral administration of RK-28 solution, the plasma concentration of RK-28 was considerably lower than that after intravenous administration through all time periods, and the absolute bioavailability was a mere 4.2%. It was presumed that a specific acid-catalized decomposition of RK-28 progressed in the stomach, and also, the absorbed RK-28 suffered first-pass effects in the liver. In contrast, the absolute bioavailability following the rectal administration of a solidified RK-28 suppository preparation was significantly increased in comparison with that obtained by other administration routes. Also, RK-28 emulsion suppositories were prepared by emulsifying various amounts of the drug with 1-hexadecanol and hydrogenated castor oil (HCO 60) at 80 degrees C, and these were administered into the rabbit rectum. The resulting absolute bioavailability was 91% for the RK-28 emulsion suppository and 86.9% for an RK-28 emulsion suppository containing small amounts of Eudispert hv. These values were better than those in rats. The rectal administration of the RK-28 emulsion suppository containing small amounts of Eudispert hv showed a preferable plasma concentration-time pattern that reflects on radiation therapy.

Administration, Oral↗
PubMed1993

Human glyoxalase I. cDNA cloning, expression, and sequence similarity to glyoxalase I from Pseudomonas putida.

Glyoxalase I (EC 4.4.1.5) catalyzes the transformation of methylglyoxal and glutathione to S-lactoylglutathione. We have isolated human cDNA clones encoding glyoxalase I from a phorbol myristate acetate-treated U937 cDNA library. This cDNA encodes a protein of 184 amino acids with a calculated M(r) of 20,719. The amino acid composition calculated from the deduced amino acid sequence agreed with that reported for glyoxalase I purified from human erythrocytes. The Escherichia coli cells carrying the expression vector of this cDNA acquired methylglyoxal resistance and the cell lysate showed the high activity of glyoxalase I. The amino acid sequence of human glyoxalase I exhibited 57% identity with Pseudomonas putida glyoxalase I at the C-terminal two-thirds, suggesting that the two enzymes may have originated from a common ancestor.

Amino Acid Sequence↗
PubMed1993

Preparation and evaluation of Eudragit gels. VI: In vivo evaluation of Eudispert rectal hydrogel and xerogel containing salicylamide.

Eudispert hv hydrogel and xerogel preparations containing salicylamide displayed sustained-release plasma profiles when compared with other conventional rectal preparations. The absolute bioavailability of salicylamide was 97.3% for the hydrogel preparation and 98.4% for the xerogel preparation. These results may arise because the gel preparation stays at the application site, the lower part of the rectum, over a fairly long period because of its bioadhesive force. Furthermore, the gastrointestinal and hepatic first-pass elimination of salicylamide can be avoided completely by rectal administration of these preparations. Visual and optical microscopic observation of rectal membranes indicated no irritation or abnormality after administration of Eudispert hv hydrogel and xerogel.

Acrylic Resins↗
PubMed1993

Skin permeation enhancement of tegafur by ethanol/panasate 800 or ethanol/water binary vehicle and combined effect of fatty acids and fatty alcohols.

The effects of vehicle and enhancer on the skin permeation of tegafur across excised hairless mouse skin were investigated. Ethanol, water, panasate 800 (tricaprylin), and their mixtures were used as vehicles, and then a series of fatty acids or fatty alcohols was employed as representative enhancers. The skin permeability of tegafur was dramatically increased by the combination of ethanol and panasate 800, whereas the combination of ethanol and water resulted in only a little increase. The greatest permeation ratio (56.8% of dose at 12 h) was obtained with the ethanol/panasate 800 (40/60) binary vehicle. Furthermore, the skin permeability of tegafur could be enhanced by the addition of fatty acids or fatty alcohols to ethanol/panasate 800 (40/60) and ethanol/water (60/40) binary vehicles. The infinite dose studies suggested that panasate 800 decreased the lag time by increasing the diffusion of tegafur, and ethanol increased the permeation rate by increasing the partition of tegafur into skin. The effects of fatty acids or fatty alcohols added to ethanol as a single vehicle were dramatic, but did not appear in the case of panasate 800 as a single vehicle. In conclusion, panasate 800 was an excellent hydrophobic vehicle in that it minimized time lag and promoted tegafur permeability combined with ethanol. This improvement was further promoted when enhancers were added.

Animals↗
PubMed1993

Effect of hydrophilic and lipophilic vehicles on skin permeation of tegafur, alclofenac and ibuprofen with or without permeation enhancers.

The effects of an ethanol/panasate 800 (tricaprylin) (40/60) system as a lipophilic vehicle, and an ethanol/water (60/40) system as a hydrophilic vehicle, with or without permeation enhancers for in vitro skin permeation and in vivo skin absorption of tegafur, alclofenac and ibuprofen with different lipophilicity, were evaluated. The in vitro and in vivo skin permeability of tegafur, alclofenac and ibuprofen was enhanced by the use of ethanol/panasate 800 (40/60) or ethanol/water (60/40) binary vehicles as a donor composition. However, the two vehicles showed contrastive properties in relation to the extent of permeation enhancement of the three drugs: tegafur > alclofenac > ibuprofen for the ethanol/panasate 800 (40/60) system, and ibuprofen > or = alclofenac > tegafur for the ethanol/water (60/40) system. When lauric acid, as a permeation enhancer, was added to both of the binary vehicles, the in vitro and in vivo skin permeability of three drugs further increased, and the in vivo absorption rate of the drugs from the ethanol/water (60/40) system was larger than that from the ethanol/panasate 800 (40/60) system. In conclusion, it was suggested that the ethanol/panasate 800 (40/60) lipophilic binary vehicle is useful for hydrophilic drugs, and conversely, the skin absorption of lipophilic drugs can be improved by the use of the ethanol/water (60/40) hydrophilic binary vehicle with or without lauric acid as a permeation enhancer.

Animals↗
PubMed1993

In vivo release of water-soluble drugs from stabilized water-in-oil-in-water (W/O/W) type multiple emulsions following intravenous administrations using rats.

The in vivo release of four water-soluble drugs, cefadroxil, cephradine, antipyrine and 4-aminoantipyrine, from a stabilizing water-in-oil-in-water (W/O/W) type multiple emulsion was studied using rats. The W/O/W type multiple emulsion used in this study could be stabilized for 30 d after preparation at room temperature and also for 24 h in pH 7.4 isotonic phosphate buffer or in rat plasma at 37 degrees C. The cefadroxil and cephradine concentrations in rat plasma following intravenous administrations of their W/O/W type multiple emulsions containing drugs were considerably prolonged compared with those of respective aqueous solutions. Sustained-releasing properties of cefadroxil and cephradine from W/O/W type multiple emulsions could be explained by the mechanism underlying the long residence time of W/O/W type multiple emulsions and delay-release of drugs from the W/O/W type multiple emulsions circulated with rat blood stream. However, antipyrine and 4-aminoantipyrine decreased rapidly following W/O/W type multiple emulsions and these plasma profiles coincided precisely with those following intravenous administration of the aqueous solutions of drugs. These in vivo releasing data correlated with in vitro drug release observation stated in the previous papers.

Amino Acids↗
PubMed1993

Effect of cytokines on the expression of cell adhesion molecule and on the adhesion of melanoma cells to endothelial cells.

We examined the role of cell adhesion molecules (CAM) by which tumor cells bind to the endothelial cells using human umbilical vein endothelial cells (HUVEC) and cultured melanoma cells. Endothelial cells from human umbilical veins were isolated and examined for CAM expression and its modulation by tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6) or interferon-gamma (IFN-gamma). The expression of intercellular adhesion molecule 1 (ICAM-1) on HUVEC was increased by TNF-alpha, IL-1 and IFN-gamma when measured by ELISA or flow cytometric (FACS) analysis. IL-6 did not increase ICAM-1 expression on HUVEC. Two melanoma cell lines, Malme-3M and SK-Mel-28, showed increased expression of ICAM-1 after treatment with TNF-alpha, IL-1 and IFN-gamma in FACS analysis. IFN-gamma induced increased expression of HLA-DR only in SK-Mel-28 melanoma cells, not in Malme-3M melanoma cells. Neither HUVEC nor melanoma cells expressed lymphocyte function-associated antigen 1 (LFA-1) in either the basal (i.e., cytokine untreated) condition or the cytokine treated condition. Melanoma cells showed minimal increment in adhesion to TNF-alpha or IL-1 treated HUVEC than to cytokine untreated HUVEC. HUVEC and melanoma cells did not express LFA-1 and increased ICAM-1 expression by TNF-alpha, IL-1 and IFN-gamma treatment in FACS analysis did not coincide with minimal increase of melanoma cells adhesion to cytokine treated HUVEC. These results suggest that adhesion between melanoma cells and HUVEC is probably mediated by molecular interaction other than ICAM-1/LFA-1.

Cell Adhesion↗
PubMed1993

Possible roles of LFA-1 and Fc gamma receptors on the functional immaturities of cord blood polymorphonuclear leukocytes.

The functional immaturity of PMNs is one of the major causes of overwhelming sepsis in newborns. In this study, we observed functions and surface markers of PMNs to investigate what causes the functional immaturity of PMNs in newborns. As results, the percentage of EA rosette forming PMNs (58.5 +/- 15.5%) and the chemotactic movement (0.14 +/- 0.09 mm) of cord blood PMNs were significantly lower than those of adult peripheral blood PMNs (70.8 +/- 9.9%, 0.60 +/- 0.34 mm). Cord blood PMNs showed decreased glass adherence and ADCC activity. The expression of Fc gamma RII or Fc gamma RIII was a little lower than those of adult peripheral blood PMNs, but the expression of Fc gamma RI (43.1 +/- 26.8%) was significantly higher than that of adult peripheral blood PMNs (3.2 +/- 1.8%). There was a significant difference in LFA-1 expression between EA rosette forming PMNs (92.9 +/- 9.1%) and EA rosette non-forming PMNs (25.6 +/- 22.6%). From these results, it is assumed that neonatal PMNs may consist of heterogeneous populations. And the relatively high percentage of EA rosette non-forming PMNs which express a low level of LFA-1 may be responsible for the functional immaturity of cord blood PMNs.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1992

Preparation and evaluation of Eudragit gels. III: Rectal gel preparations for sustained release of pentoxifylline.

A novel method was established for the preparation of Eudragit S, Eudragit L, and Eudispert high-viscosity (hv) hydrogel and xerogel preparations containing a medicinal component such as pentoxifylline (an agent that improves cerebral microcirculation). A significant correlation was found between the in vitro mean dissolution time and the in vivo mean residence time of pentoxifylline after rectal administration of these preparations in rabbits. Staying properties of the hydrogel and xerogel preparations in the lower part of the rectum were compared with those of polyethylene glycol 2000 and Witepsol S-55 suppositories in rats, with water-insoluble dye. Eudispert hv hydrogel and xerogel preparations have excellent staying properties in the rectum. The efficacy of Eudispert hv xerogel preparations may be reduced by first passage through the liver after oral administration.

Acrylic Resins↗
PubMed1992

Preparation and evaluation of Eudragit gels. IV: Rectal gel preparations for sustained release and avoidance of first-pass metabolism of propentofylline.

Formulations of a high-viscosity acrylic resin gel (Eudispert hv) containing propentofylline, a new cerebral microcirculation-improving agent, were prepared and tested for avoidance of the first-pass metabolism of propentofylline through the liver and for sustained release of propentofylline. The absolute bioavailability of propentofylline after oral administration was only 4% in rabbits. The relative bioavailabilities of propentofylline from polyethylene glycol (M(r), 2000) and Witepsol H-15 suppositories were approximately 8- and 16-fold, respectively, compared with oral administration. Furthermore, the absolute bioavailability of propentofylline from Eudispert hv hydrogel and xerogel preparations was approximately 100%. The results indicate that, in principle, drug loss caused by first-pass metabolism may be avoided completely by placing Eudispert hv hydrogel and xerogel formulations in the lower part of the rectum for long periods.

Acrylic Resins↗
PubMed1992

Preparation and evaluation of eudragit gels. V. Rectal gel preparations for sustained release and avoidance of first-pass metabolism of lidocaine.

The release of lidocaine from hydrogel and xerogel preparations was remarkably suppressed compared with polyethylene glycol (PEG) 2000 suppository. The release rate of lidocaine from hydrogel and xerogel increased with the increase in the amount of sodium hydroxide incorporated within the range of 3 to 7 milliequivalent (meq). After an oral administration of lidocaine HCl solution, the plasma concentration of lidocaine was considerably lower than that after intravenous administration for all time periods. The absolute bioavailability (F(oral)) was 5.63%. For the Witepsol S-55 and PEG 2000 suppositories, the plasma levels of lidocaine were higher than those for the oral preparation, and Cmax and area under the concentration-time curve (AUC) values significantly improved (p < 0.01). The absolute bioavailabilities were 21.3 and 29.6%, respectively. On the other hand, Eudispert hv-hydrogel and xerogel preparations showed the characteristics of a sustained-release preparation, especially the xerogel preparation with 5 meq NaOH. Absolute bioavailability for hydrogel and xerogel preparations increased significantly (p < 0.05) by approximately 1.7-3.4 folds compared with those of Witepsol S-55 and PEG 2000 suppositories.

Acrylic Resins↗
PubMed1991

Preparation and evaluation of Eudragit gels. I: Eudragit organogels containing drugs as rectal sustained-release preparations.

New organogels containing salicylic acid, sodium salicylate, procaine, and ketoprofen were prepared by using Eudragit L and S, and propylene glycol. The physical properties (e.g., penetration and extensibility) of the organogels were affected considerably by the incorporation of a basic drug, such as procaine, rather than an acidic drug, such as salicylic acid. In in vivo evaluation using rabbits, it was found that 30% Eudragit L organogels containing 1.25% (w/w) salicylic acid or 2.5% (w/w) ketoprofen showed sustained plasma salicylic acid or ketoprofen levels and almost the same AUC as compared with Witepsol H-15 suppositories containing these drugs. Furthermore, the relative bioavailability for salicylic acid and ketoprofen released from 30% Eudragit L organogels, with 10% (w/w) linolic acid or oleic acid as absorption enhancer, increased to 1.55-1.75- and 1.46-1.85-fold, respectively, compared with 30% Eudragit L organogels without these unsaturated fatty acids.

Acrylic Resins↗
PubMed1991

Preparation and evaluation of Eudragit gels. II: In vitro release of salicylic acid, sodium salicylate, and ketoprofen from Eudragit L and S organogels.

The in vitro dissolution characteristic of salicylic acid, sodium salicylate, and ketoprofen from Eudragit L and S organogels was investigated by the rotation disk method. The dissolution pattern of salicylic acid and erosion of Eudragit L polymer from the organogels followed apparent zero-order kinetics, providing strong evidence for a surface erosion mechanism and negligible diffusional release of salicylic acid. On the other hand, the dissolution of salicylic acid from Eudragit S organogels was a linear function of the square root of time. The apparent dissolution rate of salicylic acid from Eudragit S organogels increased with increasing temperature from 32 to 42 degrees C and agitation rate from 50 to 200 rpm. A linear relationship was obtained between the logarithm of apparent dissolution rate constants and the reciprocal of absolute temperatures. The activation energy for release of salicylic acid from Eudragit S organogels was in the range of 2.99 to 5.57 kcal/mol. From various experimental results, it was concluded that the release process of salicylic acid from Eudragit S organogels was diffusion controlled through the organogels matrix.

Acrylic Resins↗
PubMed1991

Isolation and cultivation of microvascular endothelial cells from rat lungs: effects of gelatin substratum and serum.

Microvascular endothelial cells from rat lungs were cultured in serum-free medium supplemented with an endothelial growth substance, insulin, hydrocortisone and so on. Five to seven days after plating, cultured cells formed a monolayer. They were identified as endothelial cells by morphology and by positive immunohistochemistry for factor VIII-related antigen, a marker for endothelia cells. Differences between gelatin coated culture plates and plastic culture plates in endothelial cell proliferation were evaluated. Cells plated on uncoated plastic plates had a spindle-shaped morphology and did not express factor VIII-related antigen. Two types of medium, serum-free medium containing endothelial growth substance and basal medium supplemented with 20% fetal calf serum, were also compared in primary culture. In contrast with the serum-free medium, cells cultured in the serum-containing medium showed fibroblast-like morphology and did not express factor VIII-related antigen. These results suggest that a gelatin substratum and serum-free medium containing endothelial growth supplement are necessary for in vitro proliferation of microvascular endothelial cells isolated from rat lungs. The culture method and conditions outlined here allow the proliferation of pure microvascular endothelial cells from rat lungs. It may be useful in studying hematogenous metastasis to the lung and the role of microvascular endothelium in other pulmonary disease.

Animals↗