• Journal of Pharmaceutical Investigation
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• v.5 no.2
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• pp.51-56
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• 1975

In the course of the investigations on drug metabolism and drug disposition in man, it has been noted that there are often rather striking individual differences in the response to drugs and in the ability to metabolize and dispose of drugs. Some of the person-to-person differences are due to environmental factors, but some have clearly demonstrated to be genetically determined. This report determined the rate of acetylation and some constants of sulfa-methizole to korean. The results are as follows: The overall removal rate of drug from the body is 0.572(k, $hr^{-1}$) the rate constant for acetylation, 0.222($k_2$, $hr^{-1}$) the rate constant for excretion of unchanged drug, 0.350($k_3$, $hr^{-1}$) and the faction of a dose ultimately excreted in the urine as unchanged drug is 0.677. And this report determined the optimal time to make a single blood level determination after an oral dose of the drug and obtain a reasonable index of the rate of sulfamethizole metabolism. The resulting data(sulfamethizole levels at 5 hours after drug administration) clearly established bimodality even though only about 106 subjects were tested.

• Toxicological Research
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• v.27 no.4
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• pp.191-203
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• 2011

There has been growing concern about the toxicity of phthalate esters. Phthalate esters are being used widely for the production of perfume, nail varnish, hairsprays and other personal/cosmetic uses. Recently, exposure to phthalates has been assessed by analyzing urine for their metabolites. The parent phthalate is rapidly metabolized to its monoester (the active metabolite) and also glucuronidated, then excreted. The objective of this study is to evaluate the toxicity of phthalic acid (PA), which is the final common metabolic form of phthalic acid esters (PAEs). The individual PA isomers are extensively employed in the synthesis of synthetic agents, for example isophthalic acid (IPA), and terephthalic acid (TPA), which have very broad applications in the preparation of phthalate ester plasticizers and components of polyester fiber, film and fabricated items. There is a broad potential for exposure by industrial workers during the manufacturing process and by the general public (via vehicle exhausts, consumer products, etc). This review suggests that PA shows in vitro and in vivo toxicity (mutagenicity, developmental toxicity, reproductive toxicity, etc.). In addition, PA seems to be a useful biomarker for multiple exposure to PAEs in humans.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.23 no.1
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• pp.1-7
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• 2010

Objective : Mercuric chloride is excreted in the urine and stool. Bangpungtongseong-san(BT) has been used commonly skin disease and has diuresis and excretion effect. This study is aimed to find out effects of Kami- bangpungtongseong-san(KBT) on the skin disease toxicated by mercury. Method : Experiment was conducted with No treated group(Normal group), Mercuric chloride subcutaneous injection group(Control group) and Kami-bangpungtongseong-san-treated group (Sample group). KBT Extracts were delivered orally in 7 days in sample group. We observed epithelial cell hyperplastic, angiogenesis, inflammatory cell infiltration of skin. For the charting the results, image analysis was taken. The result of image analysis was verified significance by Sigmaplot 2000(P<0.05). Result : This study shows an relieving epithelial cell hyperplastic, angiogenesis, inflammatory cell infiltration of exposure skin on mercuric chloride. Conclusion : According to the result of study, we can expect to the effect of KBT extracts' therapeutic action to tissue injuries of the mice' skin on acute mercurial toxication.

• Archives of Pharmacal Research
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• v.13 no.3
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• pp.227-232
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• 1990

A Physiologically based pharmacokinetic model was used to describe the distribition and elimination of cefriazone in the rat. To validate the practical application of the model, the effect of cffeine on the model was also examined. The model consisted of eleven compartments representing the major sites for ceftriaxone distribution including carcass which served as a residual compartment. Elimination was represented by renal and hepatic (metabolic biliary )excretion with GI secretion and re-absorption. The drug concentrations in most of the tissues were simulated using flow limited equations while brain levels were simulated using membrane limited passive diffusion distribution. The experimental data were obtained by averaging the concentration of drug in the plasma and tissues of five rats after i. v. injection of cefriazone 100 mg/kg without and with caffeine 20 mg/kg. The data for the amount of ceftriazone excreted in urine and gut contents were used to apportion total body clearance. HPLC with UV detection was used for the assay with 0.1-0.2 $\mu$g/ml sensitivity. The great majority of drug concentrations with and without caffeine show reasonably good agreements to the simulation results within 20%. The effect of caffeine on renal and hepatic clearances was apparent with 18.8% and 18.6% increase in the model values, respectively.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.243.1-243.1
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• 2003

The pharmacokinetics of eupatilin (an active components of Stillen, a new antigastritic agent) were investigated using UV-HPLC method. The quantitation limit of eupatilin was 10 ng/ml in plasma. After intravenous administration of eupatiln, 30 mg/kg to rats, the plasma concentrations of unchanged eupatilin declined rapidly with the mean terminal half-life of 0.101 hr. Total body clearance was 121 ml/min/kg, and fractions of dose excreted in urine and feces for 24 hr were only 2.5% and 0.919%, respectively. (omitted)

• The Korean Journal of Nuclear Medicine
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• v.37 no.6
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• pp.402-417
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• 2003

Purpose: To evaluate the use of monoclonal antibody (MoAb) as a carrier of the receptor-binding ligand the receptor mediated uptake into liver and subsequent metabolism of $^{111}In-labeled$ galactosylated MoAb-chelator conjugates were investigated and compared with those of $^{111}In$ labeled MoAb. Materials and Methods : T101 MoAb, $IgG_2$ against human lymphocytic leukemic cell, conjugated with cyclic DTPA dianhydride (DTPA) or 2-p-isothiocyanatobenzyl-6-methyl-DTPA (1B4M) was galactosylated with 2-imino-2-methoxyethyl-1-thio-${\beta}$-D-galactose and then radiolabeled with $^{111}In$. Biodistribution and metabolism study was peformed with two $^{111}In-conjugates$ in mice and rats. Results: $^{111}In-labeled$ T101 and its galactosylated conjugates were taken to the liver by the time, mostly within 10 min. However DTPA conjugate was retained longer in the liver than the 1B4M conjugate (55% vs 20% of injected dose at 44 hr). During this time, the radiornetabolite of DTPA conjugate was excreted similarly into urine (24%) and feces (17%). The radiometabolite of 1B4M was excreted primarily into feces (68%) rather than urine (8%). Size exclusion HPLC analysis of the bile and supernatant of liver homogenate showed two peaks the first (35%) with the retention time (Rt) identical to IgG and the second (65%) with Rt similar to free $^{111}In$ at 3 hr post-injection for the 1B4M conjugate, indicating that the metabolite is rapidly excreted through the biliary system. in contrast to DTPA conjugate, the small $^{111}In-DTPA-like$ metabolite was the major radioindium component (90%) in the liver homogenate as early as 3 hour post-injection, but the cumulative radioindium activity in feces was only 17% at 44 hour, indicating that the metabolite from DTPA conjugate does not clear readily through the biliary tract. Conclusion: The galactosylation of the MoAb conjugates resulted in higher hepatocyte uptake and enhanced metabolism, compared to those without galactosylation. Metabolism of the MoAb-conjugates is different between compounds radiolabled with different chelators due to different characteristics of radiometabolites generated in the liver.

• Journal of Pharmaceutical Investigation
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• v.38 no.3
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• pp.191-197
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• 2008

The purpose of the present study was to examine the pharmacokinetics and lymphatic delivery of the oligopeptide, a model peptide of X antigen epitope peptides, after the intramuscular administration of the peptide-bearing liposomes in rats. $^{14}C$-labelled peptide was used as a tracer to analyze the peptide levels in plasma, bile, urine, tissue homogenates, and lymph nodes (superior cervical nodes, brachial nodes and superior mesenteric nodes). Model peptide rapidly disappeared from the plasma by 30 min (${\alpha}$ phase) after i.v. administration, which was followed by the late disappearance. The apparent plasma half-lives ($t_{1/2({\alpha}),app}$) of the peptide at the ${\alpha}$ phase when administered at a dose of 0.2-1.0 mg/kg were about 5 min. The maximum plasma concentration ($C_{max}$) was $1.52\;{\mu}g/mL$, after the i.m. administration of the peptide at a dose of 1.0 mg/kg. The bioavailability, which was calculated from the time zero to last quantitative time, of the i.m. administered peptide was over 60%. Of the various tissues tested, the peptide was mainly distributed in the kidney after the i.m. administration. The peptide levels in the kidney 3 hr after the i.m. administration were higher than those of maximum plasma concentration ($C_{max}$). The cumulative amounts of the peptide found in the urine 72 hr after the administration of 1.0 mg/kg were 2-folder higher than those in the bile, suggesting that the peptide is mostly excreted in the urine. Moreover, the concentrations of the peptide in the lymph nodes were as high as that of the plasma and the tissues. In conclusion, the peptide concentration in the lymph nodes was maintained by 24 hr after the i.m. administration of the peptide-bearing liposomes.

• Journal of Food Hygiene and Safety
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• v.17 no.1
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• pp.20-25
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• 2002

This study was aimed to determine the urinary metabolite of profenofos, one of the organophos-phorus pesticides, as the biomarkers of exposure. Urine samples were collected fort 24 hours in metabolic cages after oral administration and dermal application of profenofos to rats. Identification of the derivatized urinary metabolite was determined by GC/MS and excretion time courses of the urinary metabolite was analyzed by GC/MS. Urinary metabolite of profenofos, 4-bromo-2-chlorophenol, was detected in rats urine both after oral administration and dermal application of profenofos. Parent compound was not detected in the experiment. In GC/MS, the mass spectral confirmation for 4-bromo-2-chlorophenol ion was identified at m/z 208.4-bromo-2-chlorophenol was excreted within 48 hours and 72 hours after oral administration and dermal application of profenofos, respectively. In this study, the same urinary metabolite of profenofos was detected both in oral and dermal exposure. Generally, excretion of the urinary metabolite after oral administration was detected faster than after dermal application. It is suggested that urinary 4-bromo-2-chlorophenol could be used as the biomarkers of exposure to profenofos.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.3
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• pp.325-335
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• 1997

Evidence for the existance of at least two subclasses of renal adenosine receptors has been presented. N-6-cyclohexyladenosine (CHA) is a relatively selective $A_1$ adenosine agonists, whereas 5'-N-ethylcarboxamidoadenosine (NECA) acts as a preferential agonist of $A_2$ adenoisne receptor. N6-(L-2-phenylisoproryl)-adenosine (PIA) almost unselectively activates both $A_1\;and\;A_2$ adenosine receptors at micromolar concentrations. During the characterization of adenosine receptor in the kidney, we have discovered a novel phenomenon, that is, an intramuscular administration of CHA for 3 days caused a diuresis and a suppression of urinary concentrating ability. To further characterize this novel phenomenon, an intramuscular administration of adenosine and other adenosine angonists, PIA and NECA, and prior treatment of adenosine antagonists, caffeine, theophylline and 1,3-diethyl-8-phenyl-xanthine (DPX) were performed. Systemic administration of CHA, PIA, and NECA for 3 days caused a suppression in heart rate, blood pressure and general motor activity without change in rectal temperature. Systemic administration of CHA, 0.5, 1 and 2 mg/kg/day, for 3 days caused a dose-dependent increase in urine volume and decrease in urinary osmolarity and free water reabsorption. This phenomenon was reversible and repeatable. Administration of adenosine (40 mg/kg/day) produced no apparent effect on the renal function, whereas PIA (2 mg/kg/day) produced an similar effect to CHA on the renal function. Systemic adminstration of NECA, 0.025, 0.05 and 0.25 mg/kg/day, for 3 days caused a dose-dependent increase in urine volume and dose-dependent increases in excreted amount of creatinine, urinary osmolarity and free water reabsorption. These renal effects of adenosine agonist were maximum at second day during the drug administration. In terms of increase in urine volume and the suppression of urinary concentrating ability, NECA was potent than CHA. Prior treatment of caffeine (50 mg/kg/day) or theophylline (50 mg/kg/day) abolished the diuretic effect of CHA, whereas DPX (50 mg/kg/day) did not affect the CHA effect. CHA, 0.5 mg/kg/day, produced no change in plasma renin activity and plasma levels of aldosterone, epinephrine, and norepinephrine. These results suggest that this novel phenomenon produced by an activation of renal adenosine receptors plays an important role in urinary concentrating mechanism.

• Applied Biological Chemistry
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• v.7
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• pp.29-33
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• 1966

This experiment was conducted to study the relationship between the energy value and the nitrogen content in the rat urine. Thirteen rats for ad libitum feeding group and 16 rats for two-meal group were employed in this experiment. The experimental period consisted of 22 days with a preliminary period of 10 days. During the last eight days of the experiment the urine was collected quantitatively. The rats fed two-meal per day excreted significantly (p<0.005) more nitrogen and energy in the urine than those fed ad libitum. A linear relationship between the energy concentration and nitrogen content was found. The urinary energy value was increased as the urinary nitrogen content was increased. A prediction equation was derived to compute the energy value from the content of nitrogen as follows: Y=8.924X+0.182 $S_{y{\cdot}x}=0.788$ where Y=urinary energy(kcal/100 ml) X=urinary nitrogen(gm/100 ml) Since the standard deviation of estimate is in small magnitude (0.788 kcal) when it is compared with the amount of intake of gross energy, digestible energy or metabolizable energy, this equation can be used safely to estimate the energy value from nitrogen content. Consequently, considerable amound of time and labor for the actual determination of energy can be saved. The ratio of energy to nitrogen was found to be 9.4 for ad adlibitum group and 8.6 for two-meal group. No significant difference between two group in this respect was observed.