• Journal of the korean academy of Pediatric Dentistry
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• v.32 no.3
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• pp.499-508
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• 2005

The purpose of this study were to evaluate the effect on the reversion of sedation induced by midazolam with flumazenil and to determine the plasma concentration of flumazenil according to the method of administration. Intranasal and intravenous flumazenil were administered to sedated health volunteers aged from 23 to 25 years, in doses typical of those used clinically to induce sedation with midazolam and for reversal with flumazenil. Objective assessment for degree of sedation and vital signs, plasma concentration were made for 2 hours period. 1. Systolic and diastolic blood pressure, $SpO_2$ were not changed by adminstration of flumazenil in sedated subject with midazolam, but pulse rate was increased temporarily. 2. Flumazenil showed the reversal of the sedative effect induced by midazolam regardless of administration methods. But intravenous administration showed more effect on the degree and the duration of reversion than intranasal administration with the exception of on set time. 3. Peak plasma concentration of flumazenil administered by intranasal route reached after 2 min and that of flumazenil administered by intravenous route was 4 min. Thus uptake of flumazenil did not showed any difference in accordance with the adminstration route. 4. Administration of flumazenil resulted in the temporary increase of midazolam plasma concentration.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7195-7200
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• 2014

Background: The aim of this study was to evaluate how CYP2C19 affects icotinib and metabolite' exposure, and to determine whether the exposure and EGFR genotype influences survival time, tumor metastasis and adverse drug reactions. Materials and Methods: 274 NSCLC patients who accepted 125mg icotinib/t.i.d. were chosen from a phase III study. Blood samples were obtained in $672^{nd}$ ($4^{th}$ week) and $1,680^{th}$ hours ($10^{th}$ week), and plasma was used to quantify the concentration of icotinib and blood cells were sampled to check the genotypes. Clinical data were also collected at the same time, including EGFR genotypes. Plasma concentrations were assessed by HPLC-MS/MS and genotype by sequencing. All data were analyzed through SPSS 17.0 and SAS 9.2. Results: CYP 2C19 genotypes affected bio-transformation from icotinib to M24 and M26, especially in poor-metabolisers. Higher icotinib concentrations (>1000 ng/mL) not only increased patient PFS and OS but also reduced tumor metastasis. Patients with mutant EGFR experienced a higher median PFS and OS (234 and 627 days), especially those with the 19del genotype demonstrating higher PR ratio. Patients who suffered grade II skin toxicity had a higher icotinib exposure than those with grade I skin toxicity or no adverse effects. Liver toxic reactions might occur in patients with greater M20 and M23 plasma concentrations. Conclusions: CYP2C19 polymorphisms significantly affect icotinib, M24 and M26 exposure. Patients with mutant EGFR genotype and higher icotinib concentration might have increased PFS and OS and lower tumor metastasis. Liver ADR events and serious skin effects might be respectively induced by greater M20, M23 and icotinib concentrations.

• Journal of Pharmaceutical Investigation
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• v.30 no.4
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• pp.241-246
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• 2000

To develop a sustained-release preparation containing ketorolac tromethamine, two sustained-release pellet formulations were evaluated with a pharmacokinetic study as compared with a conventional commercial tablets (10 mg $Tarasyn^{TM}$, Roche Korea Ltd.). Two sustained-release formulations were as follows; formulation A was composed of an inner layer containing 75% of drug coated with $Eudragit^{TM}$ RS 100 membrane and an outer layer containing 25% of drug mixed with $Eudragit^{TM}$ NE30D, and formulation B was composed of only an inner layer containing 100% of drug coated with $Eudragit^{TM}$ RS 100 membrane. The dissolution test was performed for two formulations. In case of conventional tablets, 2.5 mg of drug per a dose was administered orally into male Albino rabbit (2.0-2.3 kg of body weight) 3 times at intervals of 4 hours. In case of two sustained formulations, 7.5 mg of drug was administered once orally. Blood samples were withdrawn periodically after the administration, and the blood concentration was determined by HPLC. The conventional tablets showed very high peak-trough fluctuation between administered doses, but two sustained formulations showed less fluctuation. Formulation A with the loading dose showed the time to reach minimum effective concentration (MEC) i.e. the onset time was less than 20 min, while Formulation B had more than 1 hr of the onset time. Formulation A had the more constant plasma level than formulation B. However, formulation B had a time lag, so the plasma level was less than MEC for an initial period of 1 hr. In formulation A, the plasma level was maintained within the therapeutic window $(0.3-5\;{\mu}g/ml)$ for a long period. Formulation A was thought to be an ideal sustained-release formulation for ketorolac tromethamine oral delivery system.

• Journal of Pharmaceutical Investigation
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• v.33 no.2
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• pp.113-120
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• 2003

Drug interactions with food, on occasion, lead to serious nutritional and functional changes in the body as well as alternations of pharmacological effect. It, therefore, should be necessary to take drug interactions with food into consideration for effective and safe therapeutics. Diabetes mellitus is a heterogeneous group of disorders characterized by abnormal glucose homeostasis, resulting in hyperglycemia, and is associated with increased risk of micovascular, macrovascular, and neuropathic complications. However, the precise mechanism of diabetes mellitus remains unclear. Three basic objectives in the care of diabetic patients are maintaining optimal nutrition, avoiding hypo- or hyperglycemia and preventing complications. The purpose of this study was to investigate thε effect of Laminaria japonica diet on the absorption, distribution, metabolism and excretion of glipizide which are frequently used in the treatment of diabetes. Diabetic rats induced by streptozotocin were employed in this study. Blood concentrations of oral hypoglycemic agents were measured by HPLC and resultant pharmacokinetic parameters were calculated by RSTRIP. The mechanisms of drug interaction with food were evaluated on the basis of pharmacokinetic parameters such as $k_{a},\;t_{1/2},\;C_{max},\;t_{max}$ and AUC. Administration of glipizide in normal rats treated with Laminaria japonica diet showed significant increase in AUC, $k_{a},\;t_{1/2},\;t_{max}$ and decrease in $C_{max}$, compared to those without Laminaria japonica diet. This might result from adsorption of glipizide on components of Laminaria japonica, causing delayed absorption. Administration of glipizide in diabetic rats treated with Laminaria japonica diet showed significant increase in $t_{1/2}\;and\;t_{max}$, and decrease in $C_{max}$, compared to those without Laminaria japonica diet. This might also result from adsorption of glipizide on components of Laminaria japonica, causing delayed absorption and flattened blood concentration of glipizide. The oral glucose test showed that Laminaria japonica diet could lower blood glucose level probably through either inhibiting the activity of disaccharidases, intestinal digestive enzymes, or delaying the absorption of glucose. More studies should be followed to fully understand pharmacokinetic changes of glipizide caused by long-term Laminaria japonica diet.

• Journal of Pharmaceutical Investigation
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• v.29 no.2
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• pp.87-92
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• 1999

Drug delivery to the brain may be achieved by producing chimeric peptide, attaching the drug to protein 'vectors' which are transported into the brain from the blood by a receptor-mediated transcytosis through the blood-brain barrier (BBB). Since the BBB expresses high concentrations of transferrin receptor, and it was reported that anti-transferrin receptor mouse monoclonal antibody (OX26) undergoes transcytosis through the BBB, it is logical to assume that a drug delivery system via transferrin receptor-mediated transcytosis is a promising strategy. In the present study, therefore, we tested feasibility of several OX26 based vectors for the brain delivery of a model drug. Avidin-based delivery vectors such as OX26-streptavidin (OX26-SA), OX26-neutralite avidin (OX26-NLA) were chemically synthesized vectors and OX26 immunoglobulin G 3 type $C_{H}3$ fusion avidin $(OX26\;IgG3C_H3-AV)$ was genetically engineered. To improve the efficiency of producing chimeric peptide, we used avidin-biotin technology. Pharmacokinetics of $[^3H]biotin$ bound to OX26-SA, OX26-NLA and $OX26\;IgG3C_H3-AV$ was determined by intravenous injection technique, and their stabilities in plasma were analyzed using HPLC. The brain delivery of $[^3H]biotin$ bound to OX26-SA, OX26-NLA and OX26\;$IgG3C_{H}3-AV$ (expressed as %ID/g brain) was $0.22{\pm}0.01$, $0.18{\pm}0.01$ and $0.25{\pm}0.09$, respectively. The areas under the plasma concentration versus time curve (AUC) for OX26-SA, OX26-NLA, $OX26\;IgG3C_H3-AV$ from time zero to 60 min were $209{\pm}10$, $195{\pm}9$, $134{\pm}29\;%ID\;min/ml$ respectively and their total clearances $(CL_{tot})$ were $1.00{\pm}0.09$, $1.08{\pm}0.07$ and $1.54{\pm}0.29\;ml/min/kg$, espectively. These results showed that these vectors possess preferable pharmaceutical (e.g., resonable stability) and pharmacokinetics (e.g., significant brain uptake and enhanced AUC) for brain delivery. Therefore, these vectors may be broadly useful in the brain delivery of drugs that are not transported into the brain to a significant extent.

• Korean Journal of Clinical Pharmacy
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• v.8 no.2
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• pp.122-132
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• 1998

SB-31 which contains Pursatilla, Licoris and Ginseng extracts was recently proved as an anticancer agent. In a preclinical effort to be applied this drug to human, pharmacokinetics of SB-31 was carried out in rats and rabbits. Glycyrrhizin(GZ), a saponin of Licoris was used as a standard ingradient for the pharmacokinetics of SB-31. The rat's blood, bile and urine samples were serially collected in femoral vein, common bile duct and bladder, respectively, after bolus i.v. injection at a dose of 1 or 1/5 ampul/rat and rabbit's blood samples from the marginal ear vein at a dose of 1 or 3 amp./rabbit. GZ and glycyrrhetic acid(GA), a major metabolite of GZ in the physiological samples were analysed by HPLC with UV detection. The decline of GZ in plasma concentration was generally biexponential at each dose. GZ was almost completely recovered in bile within 18 hour. GA wasn't detected in the samples with UV detector. In the rat, Vss and Kel at a dose of 1 and 1/5 ampul of SB-31 were $98.06\pm6.07\;ml,\;0.33\pm0.05\;hr^{-1}\;and\;65.46\pm11.19\;ml,\;0.68\pm0.25\;hr^{-1}$, respectively. Those in rabbits at a dose of 3 and 1 ampul of SB-31 were $235.24\pm30.72\;ml,\;0.13\pm0.36\;hr^{-1}\;and\;341.32\pm28.58\;ml,\;0.27\pm0.04\;hr^{-1}$, respectively. 'WinNonlin' was utilized for the compartmental analysis. A two-compartment model was chosen as the most appropriate pbarmaco-kinetic model. The data were best described by using a weighting factor of $1/y^2$. To evaluate the effect of SB-31 on cardiovascular system, serially diluted SB-31 was directly injected into coronary artery in the isolated perfused rat heart and the effect of PSF, PSH, saponins of Pursatilla, and SB-31 on PT, APTT of healthy human plasma was examined. Except the positive inotropic effect of ten times diluted solution of SB-31, there was no significant effect on LVDP, (- dp/dt)/(+dp/dt), heart rate and coronary flow in comparision with that of vehicle. SB-31 had no effect on PT but slightly delayed APTT about $6.9{\sim}11.5\%$. There was no significant effect of PSF and PSH on PT & APTT. Conclusively, SB-31 did not show any notable toxic effects on cardiovascular system.

• Journal of Nutrition and Health
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• v.29 no.8
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• pp.889-898
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• 1996

This study estimated the re!ation between psychological stress and stress hormones, nu­t tritional status of patients with non-insulin dependent diabetes mellitus(NIDDM). Psycho­l logical stress such as depr'ession and anxiety in 34 diabetics was analyzedin relation to nutrient intake, blood components such as fasting blood sugar(FBS), hemoglobin AIC, stress hormones a and amino acids. The IeveIs of depression and anxiety were measured by The center for ep­i idemiological studies-depc$pm$111.49pg/ml for total catecholamine ( (norepmephrine and epinephrine) and 233.95 $pm$73.99pg/ml for norepinephrine, 94.03$pm$75. 9 97pg/ml for epinephrine, 13.lS$pm$5.55pl/dl for cortisol and 171.50$pm$62.50pg/ml for gul c cagon respectlveIy. The leveIs of stress hormones in diabetics such as total catecholamine, norep­i mephrine cortisol and glucagon were significantly higher than those in normal control. The lev­el of epmephrine was higher in diabetics but the diffierenee was not significant. The calorie m t take in diabetics was 1762$pm$292keal which is S1.4% lower than Korean recommended dietary a allowances(RDA). Calcium intake was slightly low but other nutrients intakeswere higher than R RDA. The value of fasting blood sugar(FBS), usual fasting blood sugar(usual FBS) which refteet a average FBS during 3 months and hemoglobin Al C in diabetics was 1S4.1S$pm$74.22mg/dl, 177.76$pm$42.77mg/dl and S.S4$pm$2.S2% respec디VeIy. The distribution of plasma amino acids in d diabetics was generally in the normal range. The leveI of anxiety in diabetics was positively cor­related with norepinephrine, concentration and usual FBS. The levels of glucagon, usual FBS a and hemoglobin Aj C were pOSI디veIy correlated with the branched chaimamino acid(BCM : leucme, isoleucme and valine)

• Korean Journal of Animal Reproduction
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• v.23 no.3
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• pp.205-212
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• 1999

The present study was designed to examine the effects of selenium(Se), vitamin E(Vit. E) and recombinant Bovine Somatotropin(rBST) administration on the selenium and vitamin E concentrations of blood in Hanwoo sires Hanwoo sires were randomly assigned to five groups; 1. control, 2. rBST, 0.09mg/kg body weight (BW) 3. Vit E, 1,500IU/kg BW, 4. Se 0.lmg/kg BW, 5. Vit E, 1.500IU plus Se 0.1mg/kg BW. rBST, Vit. E and Se for each experimental group were given 6 times at 15 days interval by intramuscular injection. Blood samples were collected 10 times for experimental periods, separated the serum by centrifugation, and stored at －7$0^{\circ}C$. Se and Vito E concentrations in blood were measured by fluorophotometer and HPLC. Se concentrations of blood in control, rBST, Vito E, Se and Se plus Vito E groups were 64.55, 65.50, 68.15, 73.11 and 74.09 ppb/$m\ell$, respectively. Se concentration in Vit. E plus Se group was significantly higher than in control and rBST groups (P＜0.05), but Vito E group was not significantly different in control and rBST groups(P＞0.05). The Vit. E concentrations of blood in control, rBST, Vit. E, Se and Se plus Vit. E groups were 2.27, 2.32, 2.80, 2.58 and 2.75 ppm/$m\ell$, respectively. Vit. E and Vit. E plus Se groups were slightly higher than those of any other groups, but not significantly difference in 외 I experimental groups(P＜0.05). These results indicate that Se and Vit. E concentrations of blood were slightly increased with the injection of Se and Vit. E in Hanwoo sires.

• Journal of Life Science
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• v.19 no.2
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• pp.163-168
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• 2009

To understand cytotoxic activity of Rubia cordifolia L. (Rubiaceae), which has been used as a traditional oriental medicine, the mechanism underlying cytotoxic effect of its extract on human acute Jurkat T cells was investigated. The methanol extract of roots (3 kg) of R. codifolia was evaporated, dissolved in water, and then extracted by dichloromethane. The substances in the chloroform extract showing the most cytotoxic activity were further purified by a series of preparative HPLC. The extracted active substance (65 mg) was designated as CCH1. When Jurkat T cells were treated with CCH1 at concentration ranging from 0.5 to 2.0 ${\mu}g$/ml, apoptotic phenomena of cells companying several subsequent biochemical reactions such as mitochondria cytochrome c release, activation of casapase-8, -9, and caspase- 3, degradation of PARP and DNA fragmentation occurred via mitochondria-dependent pathway. However, abrogation of apoptosis was observed in an ectopic expression of Bcl-xL, which is a suppressor for mitochondrial cytochrome c release. These results demonstrate that the cytotoxicity of CCH1 against Jurkat T cells is attributable to apoptosis mediated by mitochodria-dependent death-signaling regulated by Bcl-xL. In addition, the CCH1 is more potent to leukemia Jurkat T cell than to human peripheral blood monocyte cells (PBMC).

• Journal of the Korean Applied Science and Technology
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• v.37 no.5
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• pp.1239-1247
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• 2020

Sedum kamtschaticum Fisch., a native plant of Korea, has been used in Korean traditional medicine in the form of water extract for its capacity to improve blood circulation and for its antioxidant and anti-inflammatory effects. Since previous research suggests that S. kamtschaticum Fisch. has excellent antioxidant and mushroom tyrosinase inhibition activities, in this study, the root and stem parts of S. kamtschaticum Fisch. are extracted in 70% ethanol (SKS, SKR), fractionated with and in order of n-hexane (SSH), ethyl acetate (SSE, SRE), chloroform (SSC, SRC) and water (SSW, SRW) according to the polarity of each solvent, and tested for its applicability as a cosmetic material. According to the total polyphenol, flavonoid contents and DPPH radical scavenging activity of each fraction, the contents and scavenging activity of the root extractions (SKR) were higher than those of the stem extractions (SKS), ethyl acetate fractions (SSE, SRE) being the most effective. In addition, ethyl acetate fractions had the highest tyrosinase inhibition activity and melanin synthesis inhibition activity used on B16F10 melanoma cells, at the concentration of 10 ㎍/mL. HPLC analysis detected a variety of polyphenols including gallic acid and quercetin. This study suggests the potential role of S. kamtschaticum Fisch. as a natural cosmeceutical material.