• Korean Journal of Clinical Pharmacy
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• v.9 no.1
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• pp.66-70
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• 1999

The effect of circadian rhythm on cyclosporine pharmacokinetics was studied in rabbits after oral administration of 10 mg/kg dose of cyclosporine at 10:00 a.m. and 10:00 p.m. The blood concentration data were subjected to simultaneous computer nonlinear least squares regression analysis using a 1-compartment pharmacokinetic model. The blood concentrations of cyclosporine at 10:00 a. m. were increased significantly during 2-6 hr compared to those at 10:00 p.m. The area under the blood concentration-time curve (AUC) and peak concentration $(C_{max})$ of cyclosporine at 10:00 a.m. were increased significantly compared to those at 10:00 p.m. The mean total body clearance (CL) of cyclosporine at 10:00 a.m. were decreased significantly compared to those at 10:00 p.m. It is reasonable to consider individual circadian rhythm for effective dosage regimen of cyclosporine in therapeutics.

• Investigative Magnetic Resonance Imaging
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• v.17 no.4
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• pp.259-266
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• 2013

Purpose : To investigate the blood pharmacokinetics and bio-distribution of DTPA-bis-amide (L3) Gd(III) complexes. Materials and Methods: The pharmacokinetics and bio-distribution of Gd $(L3)(H_2O){\cdot}nH_2O$ were investigated in Sprague-Dawley rats after intravenous administration at a dose of 0.1 mmol Gd/kg. The Gd content in the blood, various tissues, and organs was determined by ICP-AES. Blood pharmacokinetic parameters were calculated using a two-compartment model. Results: The half-lives of ${\alpha}$ phase and ${\beta}$ phase Gd $(L3)(H_2O){\cdot}nH_2O$ were $2.286{\pm}0.11$ min and $146.1{\pm}7.5$ min, respectively. The bio-distribution properties reveal that the complex is mainly excreted by the renal pathway, and possibly excreted by the hepatobiliary route. The concentration ratio of Gd (III) was significantly higher in the liver and spleen than in other organs, and small amounts of Gd (III) ion were detected in the blood or other tissues of rats only after 7 days of intravenous administration. Conclusion: The MRI contrast agent Gd $(L3)(H_2O){\cdot}nH_2O$ provides prolonged blood pool retention in the circulation and then clears rapidly with minimal accumulation of Gd(III) ions. The synthesis of gadolinium complexes with well-balanced lipophilicity and hydrophilicity shows promise for their further development as blood pool MRI contrast agents.

• The Korean Journal of Physiology
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• v.1 no.1
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• pp.23-32
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• 1967

Disappearance rate of injected $D_2O$ from the arterial blood as well as the effect of histamine on the rate were studied in rabbits. The concentrations of $D_2O$ in the serial arterial samples obtained through a Polyethylene tubing inserted into the carotid artery were assayed by the freezing point elevation method of Reaser. At zero time 3 ml of isotonic $D_2O$ in normal saline was injected into the jugular vein and at the same time serial sampling of arterial blood started. The serial sampling interval was either 7.7 sec or 12.3 sec. In the histamine treated animals histamine diphosphate (0,5 mg of histamine base) was injected intravenously 30 minutes prior to the zero time. The following results were obtained. 1. $D_2O$ concentration in arterial plasma water, x, was empirically obtained by the sum of 2 exponential terms of time, $x=Ae^{-k1t}+Be^{-k2t},$ and its theoretical basis was sought. The first term of the right member of the equation was regarded to be attributable to the compartment P which possessed instantaneous exchange of water with plasma. The second term was postulated to represent the poorly exchangeable compartment. 2. The constant A of the equation was evaluated as 4,37% and 14.3% in the control and histamine treated groups, respectively. B was 1.19% in the control and 0.849% in histamine treated animals. 3. The disappearance rates determined were; $k_1=0.0519{\pm}0.0221\;sec^{-1}\;K_2=0.00454{\pm}0.00247\;sec^{-1}$ in the control group. $k_1=0.1137{\pm}0.0290\;sec^{-1}\;K_2=0.00499{\pm}0.00204\;sec^{-1}$ in the histamine group. 4. In the histamine treated animals the disappearance rate of the first term was larger than that of the control animals, suggesting an enlarged size of the rapidly exchangeable compartment with regard to the plasma water. On the other hand the constant B was decreased by histamine administration, suggesting a distribution of $D_2O$ in an enlarged volume. This view was also made clear by comparing the apparent asymptotes to which the concentration curves of $D_2O$ approached in respective groups. The asymptotes in the histamine treated group showed lower values.

• Journal of Pharmaceutical Investigation
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• v.13 no.2
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• pp.51-58
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• 1983

In order to elucidate the effects of Panax Ginseng on the pharmacokinetic parameters of nalidixic acid in a patho-physiological changes, the kinetics of the disappearance of the drug from the blood, appearance in the bile and urinary excretion were studied in $CCl_4-toxicated$ rabbits. The pharmacokinetics of the drug nalidixic acid in rabbits were modeled by a two compartment. Total saponin, water extract from Panax Ginseng, significantly decreased biliary and urinary excretion of nalidixic acid.

• Journal of Fisheries and Marine Sciences Education
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• v.25 no.5
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• pp.1079-1087
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• 2013

The pharmacokinetics of florfenicol (FF) after oral administration was studied in the cultured olive flounder, Paralichthys olivaceus, using high performance liquid chromatography (HPLC). After single administration of FF (20 mg/kg body weight) by oral route in olive flounder ($700{\pm}50$ g, $23{\pm}1.5^{\circ}C$), the concentration in the serum was determined at 1, 5, 10, 15, 24, 30, 50 and 168 h post-dose. The kinetic profile of absorption, distribution and elimination of FF in serum were analyzed fitting to a two-compartment model by WinNonlin program. The area under the concentration-time curve (AUC), maximum concentration ($C_{max}$), time for maximum concentration ($T_{max}$) and elimination time were 22.51 ${\mu}g{\cdot}h/mL$, 0.84 ${\mu}g/mL$, 8.62 h and 447 h, respectively. The results of this study related to dosage and withdrawal times could be used for prescription of FF in field for the treatment of bacterial diseases in olive flounder.

• Korean Journal of Veterinary Research
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• v.35 no.3
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• pp.471-480
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• 1995

The purpose of this experiment was to develop a simple and reliable HPLC method for the detection of ciprofloxacin in chicken serum and to provide a basic data on pharmacokinetic parameters after oral and intramuscular administration. The results obtained were as follows: 1. 0.2% meta-phosphoric acid: acetonitrile(7:3, v/v) solution had a high and regular recovery rates and was selected as an extraction solution. 2. The recovery rates of ciprofloxacin were 83-97% with the selected solution in chicken serum and the detection limit was 50ng/ml in serum. 3. Ka(abosorption rate constant) were 3.652 1/h in fasted group and 0.880 1/h in non-fasted group, and Ke (elimination rate constant) were 0.061 1/h and 0.133 1/h, respectively. 4. The highest concentration in serum after intramuscular injection was 840ng/ml within 15-30min and 160-324ng/ml in 1.1-3.2 hours after oral administration. 5. The time course of blood concentration fits well into a 2 compartment model. 6. On oral administration of ciprofloxacin with feed, ciprofloxacin was absorbed more slowly and the amount of absorbed was smaller than that of in fasted chickens. 7. Blood concentration of ciprofloxacin increased in a dose-dependent manner after intramusclular and oral administraiton.

• The Korean Journal of Pharmacology
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• v.31 no.2
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• pp.251-259
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• 1995

Pharmacokinetics and pharmacodynamics of metoprolol, a selective beta-l blocker, were examined for 360 minutes after intravenous bolus administration of metoprolol to 6 dogs. Plasma concentration and excreted amount in the urine metoprolol were measured by liquid chromatography with fluorescence detection. PR interval and heart rate were measured by ECG monitoring. Blood pressure was monitored through intraarterial catheter in femoral artery and cardiac output by thermodilution method using Swan-Ganz catheter. To analyze the effect site concentration-response relationship, plasma concentration and pharmacological effects were simultaneously fitted to a two pharmacokinetic compartment linked to pharmacodynamic model with NONLIN program. Results are as follows. 1) The plasma concentration of metoprolol after intrvenous injection decreased biexponentially. The terminal half-life estimated was $1.33{\pm}0.40$ hours and the volume of distribution at steady state (Vdss) and the total body clearance were $1.04{\pm}0.4\;L/kg,\;6.55{\pm}2.21\;L/hr$, respectively. The central compartment volume of distribution and peripheral compartment volume of distribution were $0.35{\pm}0.14L/kg\;and\;0.69{\pm}0.34L/kg$. The renal clearance and intercompartment clearance were $0.53{\pm}0.25\;L/min\;and\;0.35{\pm}0.19\;L/min$. 2) Simulated biophase concentration-response curve shows hyperbolic relationship and the estimated concentration-effect relationship was best explained by Emax model when the prolongation of PR interval and the reduction of the heart rate were used as pharmacodynamic parameters. Emax and EC50 were estimated to be $26.3{\pm}4.7\;msec\;and\;88.8{\pm}82.3\;g/ml$ for PR interval, and $48.7{\pm}18.8\;beats/min\;and\;113.5{\pm}78.7\;ng/ml$ for heart rate, respectively. 3) The changes of cardiac output-effect site concentration relationship was best fitted by a linear model and the slope of the relationship was $0.005{\pm}0.003$. Diastolic blood pressure-effect site concentration relationship was also explained by the linear model and the slope of the relationship was $0.038{\pm}0.034$.

• Asian-Australasian Journal of Animal Sciences
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• v.3 no.1
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• pp.47-52
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• 1990

During prolonged exposure to the sun for 8 h each day for 10 days in which the highest ambient temperature around 14:00 h was $39^{\circ}C$, buffaloes exposed to the sun without shade increased the turnover of body water by 35% and 76% on day 5 and day 10 of exposure respectively. The total body water markedly decreased on day five and this amount was maintained thereafter. Plasma and blood volumes did not change significantly on day five but markedly decreased on day 10. Packed cell volume significantly decreased on day five and day 10 of the exposure period. The reduction of packed cell volume on day 10 coincided with the decrease in total plasma water. On day 10 of the exposure, an increase in the rate of liquid flow from the rumen was noted. It is concluded that on the fifth day of exposure, the increase in the evaporative cooling process was attributed to initial mobilization of water from the intracellular compartment. The reduction of both plasma and cell volumes occurring from day five to day 10 indicated a loss of body water from both intracellular and extracellular compartments.

• Archives of Plastic Surgery
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• v.35 no.4
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• pp.360-366
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• 2008

Purpose: Botulinum toxin type A(BoTA) can block the release of vasoconstriction cotransmitters as well as acetylcholine in nerve terminal. The authors observed that BoTA increases flap survival by preventing sympathetic collapse of peripheral vessels. Methods: 10 Sprague Dawley rats were divided into control(n=5), and BoTA group(n=5). $3{\times}10cm$ sized random pattern cutaneous flaps were elevated on the dorsal side in both groups. In BoTA group, BoTA was injected into the flap via intradermal to subdermal route, 7 days before the flap elevation. Flap survival rates (survival area/total area) were measured 7 days after the elevation. Cutaneous blood flow was measured in proximal, middle and distal compartments of the flap using laser Doppler flowmetry initially, preoperatively, at immediate postoperation, and 7 days after flap elevation, respectively. Histological examination was performed 7 days after the flap elevation. The number and shape of the vessels were evaluated under microscope. Results: Mean flap survival was $53.18{\pm}6.58%$ in control group and $93.79{\pm}6.06%$ in BoTA group, displaying statistically significant difference(p=0.0008, p<0.05). In the control group, blood flow to the middle and distal compartments of the flap decreased significantly immediately after flap elevation. In the BoTA group, blood flow to the middle compartment did not decrease(p=0.002) and slightly decreased in the distal compartment(p=0.001). Cutaneous blood flow was significantly higher in all compartments of the flap in BoTA group than in control group, 7 days after the flap elevation. In histopathologic examination, greater number of vessels were noted in the BoTA group than in the control group. Conclusion: Botulinum toxin A can increase the survival of the random pattern cutaneous flap in rats by preventing the sympathetic collapse of peripheral vessels.

• The Korean Journal of Nuclear Medicine
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• v.33 no.1
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• pp.1-10
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• 1999

Cancer cells are known to show increased rates of glycolysis metabolism. Based on this, PET studies using F-18-fluorodeoxyglucose have been used for the detection of primary and metastatic tumors. To account for this increased glucose uptake, a variety of mechanisms has been proposed. Glucose influx across the cell membrane is mediated by a family of structurally related proteins known as glucose transporters (Gluts). Among 6 isoforms of Gluts, Glut-1 and/or Glut-3 have been reported to show increased expression in various tumors. Increased level of Glut mRNA transcription is supposed to be the basic mechanism of Glut overexpression at the protein level. Some oncogens such as src or ras intensely stimulate Glut-1 by means of increased Glut-1 mRNA levels. Hexokinase activity is another important factor in glucose uptake in cancer cells. Especially hexokinase type II is considered to be involved in glycolysis of cancer cells. Much of the hexokinase of tumor cells is bound to outer membrane of mitochondria by the porin, a hexokinase receptor. Through this interaction, hexokinase may gain preferred access to ATP synthesized via oxidative phosphorylation in the inner mitochondria compartment. Other biologic factors such as tumor blood flow, blood volume, hypoxia, and infiltrating cells in tumor tissue are involved. Relative hypoxia may activate the anaerobic glycotytic pathway. Surrounding macrophages and newly formed granulation tissue in tumor showed greater glucose uptake than did viable cancer cells. To expand the application of FDG PET in oncology, it is important for nuclear medicine physicians to understand the related mechanisms of glucose uptake in cancer tissue.