• Journal of Pharmaceutical Investigation
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• 제5권2호
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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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• 제27권4호
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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.

• 한방안이비인후피부과학회지
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• 제23권1호
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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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• 제13권3호
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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.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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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)

• 대한핵의학회지
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• 제37권6호
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• pp.402-417
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• 2003

목적: 종양의 진단과 치료에 널리 이용되고 있는 단클론항체를 수용체에 결합하는 수송체로 이용할 수 있는지에 대한 가능성 여부를 평가하기 위하여, 간의 asialoglycoprotein 수용체에 결합할 수 있는 갈락토즈접합 단클론항체를 $^{111}In$로 표지하여 체내에서의 분포와 간을 중심으로 한 체내대사를 분석하였고, 그 결과를 갈락토즈를 접합하지 않은 $^{111}In$ 표지 항체와 비교하였다. 재료 및 방법: 인체 림프 구성백혈병 세포에 대한 T101 단일클론항체를 cyclic DTPA dianhydrate(DTPA) 나 2-p-isothiocy-anatobenzyl-6-methyl-DTPA(IB4M) 로 접합하고 갈락토즈를 붙인후 $^{111}In$으로 표지하였다. 생쥐와 흰쥐에서 갈락토즈를 접합한 화합물과 접합하지 않은 화합물의 체내분포와 간대사를 비교분석하였다. 결과: $^{111}In$ 표지 T101항체와 갈락토즈 접합체는 투여량의 대부분이 10분 이내에 간에 섭취되었다. DTPA 접합자를 사용한 경우 IB4M 접합자를 사용한 경우보다 간에 오랫동안 저류되어 주사 후 44시간 간 섭취율이 각각 55%와 20% 였다. 이 기간동안의 DTPA화합물의 방사성 대사산물은 24%가 소변으로 17%가 대변으로 배설되어 유사하였으나 IB4M 화합물은 68%가 대변으로 8%가 소변으로 배설되어 배설경로에 차이가 있었다. 1B4M화합물을 주사후 3시간의 담즙과 간 현탁액을 HPLC로 분석한 결과 IgG와 저류시간(Rt)이 같은 첫 절정에 35%,유리 $^{111}In$과 유사한 절정의 Rt에 65%가 관찰되어 대사산물이 빠르게 답즙으로 배출됨을 알 수 있었고, DTPA 화합물 주사후 3시간 대사산물은 90%가 $^{111}In-DTPA$와 유사한 Rt의 절정을 보였다. 그러나 대변의 $^{111}In$ 의 축적량은 낮아 DTPA 접합화합물은 담도를 통한 빠른 배설이 일어나지 않음을 알 수 있었다. 결론: 단일클론항체에 갈락토즈를 접합한 경우보통의 항체에 비하여 간 섭취가 많고, 간에서의 대사가 촉진된다. 이 경우 사용되는 접합자의 선택에 따라서 대사산물의 성분이 달라지고 간에서의 제거도 차이가 있다. 이러한 대사의 차이점은 향후 종양세포나 조직의 탐색에 이용할 방사능 표지 항체의 제조에 응용될 수 있을 것이다.

• Journal of Pharmaceutical Investigation
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• 제38권3호
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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.

• 한국식품위생안전성학회지
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• 제17권1호
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• pp.20-25
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• 2002

흰쥐를 이용하여 profenofos의 경구투여 및 피부도포 후 뇨 중 대사물질과 뇨 중 대사물질의 시간별 배설량을 GC/MS로 측정한 결과는 다음과 같다. Profenofos를 경구투여 후 뇨 중 대사물질은 4-bromo-2-chloropheno이며, GC/MS로 분석한 결과 4-bromo-2-chlorophenol는 m/z=208에서 분자이온을 추정하였다. Profenofos를 피부도포 후 뇨 중 대사물질은 경구투여와 동일한 대사물질인 4-bromo-2-chloropheno이었다. 모 화합물이나 4-bromo-2-chlorophenol외 다른 대사물질은 검출되지 않았다. Profenofos를 경구투여 후 뇨 중 대사물질인 4-bromo-2-chlorophenol의 시간별 배설량은 12시간에 가장 많은 양이 배설되었다. 또한 48시간 내 95%가 배설되었고 72시간 이후는 대사물질이 배설되지 않았다. 한편 profenofos를 피부도포 후 뇨 중 대사물질인 4-bromo-2-chlorophenol의 시간별 배설량은 12시간에 가장 많은 양이 배설되었으며, 48시간 내 87%가 배설되었고 96시간 이후는 대사물질이 배설되지 않았다. Profenofos 의 뇨 중 대사물질인 4-bromo-2-chlorophenol는 profenofos의 생체모니터링 지표물질로서 사용될 수 있을 것이라고 생각되며, 뇨 중 4-bromo-2-chlorophenol의 시간별 배설량을 측정한 결과 경구투여보다 피부도포 후 배설이 지연된 다는 것을 알 수 있었다.

• The Korean Journal of Physiology and Pharmacology
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• 제1권3호
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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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• 제7권
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• pp.29-33
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• 1966

이 시험(試驗)은 쥐오줌의 energy value와 nitrogen content와의 관계(關係)를 연구(硏究)하기 위하여 행(行)하여졌다. 이 시험(試驗)을 위하여 ad lib.구(區)에 13 마리, 2 meals구(區)에 16 마리, 도합(都合) 29 마리의 쥐가 쓰였다. 오줌의 채집(採集)은 22 일간(日間)의 본시험기간중(本試驗期間中) 8 일(日)동안 행(行)하였다. 1 일(日) 2회(回) 채식(採食)시킨 쥐들이 훨씬 많은 (p<0.05) nitrogen 을 배설(排泄)했고 아울러 더 많은 energy를 배설(排泄)하였다. 쥐오줌의 energy concentration과 nitrogen content 사이에는 직선관계(直線關係)가 있어서 nitrogen 함량(含量)이 증가(增加)하면 energy의 배설량(排泄量)이 증가(增加)된다는 사실(事實)이 밝혀 졌다. urinary nitrogen(X, gm/100 ml)으로 부터 energy value (Y, kcal/100 ml)를 산출(算出)할 수있는 공식(公式)을 유도(誘導)했는데 다음의 식(式)은 일반적(一般的)으로 이 목적(目的)을 위하여 쓰여질 수 있는 것으로 본다. Y=8.924X+0.182 (Y=urinary energy, X=urinary N) 이러한 산출(算出)에 수반(隨伴)도는 표준오차(標準誤差)는 0.788 kcal이다. nitrogen content로부터 energy concentration을 산출(算出)하는데 따르는 오차(誤差)가 이렇게 적기 때문에 또 urinary energy의 함량(含量)이 GE, DE, ME, 섭취량(攝取量)에 비(比)해 적기 때문에 유사(類似)한 Diet를 공급(供給)하는 경우(境遇) 이 식(式)은 쥐오줌의 energy value를 산출(算出)하는데 쓰일 수 있을 것이다. 따라서 오줌의 energy value의 직접측정(直接測定)에 소요(所要)되는 많은 시간(時間)과 노력(努力)이 절약(節約)되는 것이다. 쥐오줌의 energy: nitrogen의 비(比)는 9.4(ad lib.구(區)) 내지(乃至) 8.6(2 meals 구(區))으로서 채식회수(採食回數)는 이 비율(比率)에 하등(何等)의 영향(影響)이 없음이 밝혀졌다.