• 대한핵의학회지
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• 제4권2호
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• pp.11-27
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• 1970

간경변증(肝硬變症) 환자(患者) 29 례(例)에서 혈장량(血漿量), 심박출량(心搏出量) 및 신혈장류량(腎血漿流量)을 동시(同時)에 측정(測定)하여 혈역학적(血力學的) 변화(變化)를 관찰(觀察)하였으며 다음과 같은 결론(結論)을 얻었다. 1. 평균(平均) 혈장량(血漿量)은 $3793{\pm}895ml$로 정상(正常)보다 증가(增加)된 것을 보았고 혈액량(血液量)($5266{\pm}1222ml$) 및 체중(體重) kg당(當) 혈액량(血液量)($95.7{\pm}23.41ml$)도 역시(亦是) 증가(增加)되어 있었다. 체중(體重) kg당(當) 혈장량(血漿量)($69.1{\pm}19.1ml$)은 증가(增加)하는 경향(傾向)을 보였고 혈액량(血液量)과 혈장량(血漿量)의 차(差), 즉(卽) 적혈구질량(赤血球質量)은 $26.4{\pm}7.05ml$로 정상범위내(正常範圍內)에 있었다. 2. 평균(平均) 심박출량(心搏出量)은 $7708{\pm}2652ml/min$로 증가(增加)되어 있었으며 심계수(心係數)($4924{\pm}1998ml/min/M^2$) 심박동량(心搏動量) ($96.2{\pm}34.2ml/beat$), 심박동계수(心搏動係數)($62.3{\pm}27.34ml/M^2$) 및 분별심계수(分別心係數)($1.54{\pm}0.577$)도 모두 증가(增加)함을 보았다. 전말초저항(全末梢抵抗)은 $1664{\pm}753.8dynes\;sec\;cm^{-5}M^2$로 정상(正常)보다 감소(減少)되어 있었다. 3. 평균(平均) 신혈장류량(腎血漿流量)은 $537{\pm}146.8ml/min/1.73M^2$로 정상(正常) 내지는 감소(減少)된 것을 보였고, 평균(平均) treatinine clearance는 $66.7{\pm}23.0ml/min/1.73M^2$로 현저(顯著)한 저하(低下)를 보았다. filtration fraction은 일정(一定)치 않았으나 대부분(大部分)의 예(例)에서 감소(減少)되었다. 심박출량(心搏出量)의 신분별치(腎分別値)는 상대적(相對的)으로 감소(減少)하여 있었다. 4. 신혈장류량(腎血漿流量)은 전반적(全般的)으로는 정상(正常) 또는 저하(低下)되어 있었으나 creatinine clearance가 $60ml/min/1.73M^2$ 이하(以下)인 군(群)과 치료(治療)에 저항(抵抗)하는 복수군(腹水群) 및 질소혈증(窒素血症)이 있는 예(例)에서 현저(顯著)한 감소(減少)를 보였다. 5. 본실험(本實驗)에서 관찰(觀察)한 사구체(絲球體) 여과율(濾過率)의 감소(減少), filtration fraction의 저하(低下) 및 심박출량(心搏出量)의 신분별치(腎分別値)의 감소등(減少等)은 신장(腎臟)의 수입세동맥저항(輸入細動脈抵抗)의 상승(上昇)을 뒷받침한다. 6. 간경변증(肝硬變症)에서 신순환(腎循環) 장애(障碍)는 질소혈증(窒素血症)이나 핍뇨(乏尿)에 선행(先行)하여 일어남을 알 수 있었다. 7. 임상상(臨床像)이나 간기능(肝機能) 성적(成績)은 이들 혈역학(血力學) 변화(變化)와 상관관계(相關關係)가 없었고 다만 식도(食道) 정맥류(靜脈瘤)가 심박출량(心搏出量)이 증가(增加)된 예(例)에서 관찰(觀察)되었다. 8. 신혈역학(腎血力學) 변화(變化)와 혈장량(血漿量) 혹(或)은 심박출량(心搏出量) 간(間)에도 상관관계(相關關係)는 없었다.

• Toxicological Research
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• 제4권1호
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• pp.1-12
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• 1988

In order to evaluate the effect of cigarette smoking on the pharmacokinetics of theophylline in Koreans, doses of 4.5 to 5.0 mg/kg of theophylline, as injectable aminophylline, were administered to 12 normal young volunteers (male, 22 to 35 yrs;mean, 26 yrs) through intravenous infusion over 30 minutes, and pharmacokinetics of theophylline were tested. Among subjects, six were nonsmokers and the other were smokers (range 1 to 2 packs/day). Also the correlations between plasma and saliva theophylline concentrations were investigated by determining the concentrations of theophylline in saliva simultaneously at each plasma sampling time. The total body clearances of theophylline in smokers (Mean${\pm}$SD, 0.0578${\pm}$0.0092 L/hr/kg)were appreciably higher than thoxe of nonsmokers (Mean${\pm}$SD, 0.0359${\pm}$0.0063 L/hr/kg), and the half-lives of theophylline in smokers averaged 5.36${\pm}$1.22hr, and significantly shorter than those of nonsmokers which averaged 9.14${\pm}$1.73hrs(p<0.005). But the apparent volumes of distribution of theophylline did not show any significant difference between smokers (Mean${\pm}$SD,0.44 ${\pm}$0.05L/kg) and nonsmokers (Mean${\pm}$SD, 0.46${\pm}$0.05L/kg). The average concentration ratios in saliva and plasma were 0.61 in smokers and 0.56 in nonsmokers after 2 hrs following drug administrations, and the smoker group had a slightly higher value of ratio(S/P) than the nonsmoker group (p<0.05). The correlations between saliva and plasma theophylline concentration in smokers were r=0.852(p<0.0005) within 2 hr and r=0.985(p<0.0005) after 2 hrs and also those of nonsmokers were r=0.729(p<0.0005) within 2 hrs and r=0.957(p<0.0005) after 2 hrs starting the infusion. From the results, it was found that smoking cigarettes had significantly increased the clearance of theophylline and that the relationships between saliva and plasma theophylline concentrations in all subjects were better after 2 hrs than within 2 hrs starting the infusion of aminophlline.

• Tuberculosis and Respiratory Diseases
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• 제47권4호
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• pp.442-450
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• 1999

연구배경 : 한국인 결핵환자에서 의사나 병원마다 다양하게 처방되는 isoniazid(INH)와 rifampicin(RFP)의 일일용량은 외국에서 추천하는 용량과 다른 실정이라, 4제 병용요법을 시행받는 결핵환자에서 INH와 RFP의 약물동력학을 알아보고 이를 토대로 결핵환자에서 INH, RFP의 적정 일일용량을 평가하고자 본 연구를 시행하였다. 대상 및 방법 : 1997년 12월부터 1998년 7월까지 삼성서울병원에 입원하여 활동성 결핵으로 확진된 환자를 대상으로 INH 300mg, RFP 450mg, EMB 800mg, PZA 1500mg을 아침 식전 30분에 복용하고 0, 0.5, 1, 1.5, 2, 4, 6, 8, 12시간째에 채혈을 시행하여 혈청에서 INH, RFP의 농도를 측정하였고 소변은 12시간동안 4시간 간격으로 모아서 양을 기록하고 농도를 측정하였다. INH, RFP의 농도측정은 high-performance liquid chromatography(HPLC)를 이용하였다. 결 과 : 대상환자는 INH 15명, RFP 17명이었고 연령의 중앙값은 33세(24~57), 평균 체중은 $58.3{\pm}13kg$(41.9~84.5)이었으며 남녀비는 9 : 8이었다. 1) INH 결과 INH의 $7.63{\pm}3.20{\mu}g/ml$, $0.73{\pm}0.22hr$, 혈중반감기는 $2.12{\pm}0.84hr$, Ke값은 $0.83{\pm}0.15hrs^{-1}$이었으며 AUC는 $21.87{\pm}13.37{\mu}g^*hr/ml$, Xu는 $56.22{\pm}31.46{\mu}g$/24hrs 였다. CLtot은 $17.54{\pm}8.89L/hr$, CLnr은 $14.74{\pm}8.35L/hr$, CLr은 $2.79{\pm}1.31L/hr$로서 대부분이 간으로 대사되었다. 2) RFP 결과 RFP의 Cmax는 $8.93{\pm}3.98{\mu}g/ml$, Tmax는 $1.76{\pm}1.13hr$, 혈중반감기는 $2.27{\pm}0.54hr$였고 Ke값은 $0.32{\pm}0.08hrs^{-1}$이었으며 AUC는 $36.52{\pm}14.19{\mu}g^*hr/ml$, Xu는 $31.18{\pm}13.69{\mu}g$/24hrs 였다. CLtot는 $14.63{\pm}6.60L/hr$였고 CLr 이 $1.04{\pm}0.55L/hr$, CLnr이 $13.59{\pm}6.21L/hr$로서 대부분이 간으로 대사되었다. 3) 환자 체중과 최고혈중농도의 상관관계는 INH의 경우 r=-0.514, p-value>0.05이었고, RFP의 경우 r=-0.662, p-value<0.01이었다. 결 론 : INH, RFP, EMB, PZA 병용요법으로 치료받는 결핵환자에서 RFP은 체중에 따른 용량 조절이 필요하며, INH는 하루 300mg 투여로도 이상적인 최고혈중농도에 도달하지만 한국인에서 INH 하루 400mg보다 300mg이 적당할 지 여부는 향후 임상연구가 필요하리라 사료된다.

• 한국임상수의학회지
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• 제23권2호
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• pp.87-90
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• 2006

본 연구는 록시스로마이신의 정맥주사 후 육계에서의 약물동태학적 특성을 조사한것으로, 이때 록시스로마이신은 체중당 20 mg/kg 용량으로 정맥주사하였다. 시간에 따라 채혈하여 혈장을 분리한 후 액체크로마토그래프/질량분석기를 이용하여 혈장내 록시스로마이신의 농도를 측정하였다. 혈장내 록시스로마신 농도-시간 그래프의 분석은 two-compartment open model을 적용하는 것이 가장 적합하였다. 육계에서의 록시스로마이신의 약물동태학적 부변수의 값은 다음과 같았다. 소실 반감기 =$5.83{\pm}1.79h$, 평균체류 =$6.33{\pm}0.32h$, 청소율 =$0.55{\pm}0.15L/h/kg$ 및 정상상태 분포용적 = $3.47{\pm}0.84L/kg$ 육계에서 정맥주사 후 록시스로마이신은 늦은 소실과 체내 고른 분포의 약물동태학적 특성을 나타내었다. 록시스로마이신의 육계에 적용할 때에는 약물제형, 최적 용량용법, 임상효과 및 반복투여에 대한 내성등의 연구가 추후 요구된다.

• Archives of Pharmacal Research
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• 제25권6호
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• pp.973-977
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• 2002

The pharmacokinetic of paclitaxel (1 mg/kg, i.v.) was investigated in rabbits with carbon tetrachloride-induced hepatic failure. The area under the plasma concentration-time curve (AUC) of paclitaxel was significantly (p<0.01) increased in severe carbon tetrachloride-induced hepatic failure rabbits ($1364.54{\pm}382.07$ ng/ml$\cdot$hr) compared to that of normal rabbits ($567.52{\pm}141.88$ ng/ml$\cdot$hr), but not significantly in moderate carbon tetrachloride-induced hepatic failure rabbits ($803.1{\pm}208.81$ ng/ml$\cdot$hr). The volume of distribution (Vd) (6.25$\pm$1.56 L) and the elimination rate constant($\beta$) ($0.09{\pm}0.025{\;}hr^{-1}$) of paclitaxel in severe carbon tetrachloride-induced hepatic failure rabbits were significantly (p<0.05) decreased compared to those of normal rabbits ($11.65<{\pm}2.91$L, $0.12{\pm}0.030{\;}hr^{-1}$), but not significantly in moderate carbon tetrachloride-induced hepatic failure rabbits ($9.46{\pm}2.37$ L, $0.10{\pm}0.026{\;}hr^{-1}$). Total body clearance ($CL_t$) of paclitaxel in severe carbon tetrachloride-induced hepatic failure rabbits ($0.733{\pm}0.183$ L/hr/kg) was significantly (p<0.01) decreased compared to that of normal rabbits ($1.762{\pm}0.440$ L/hr/kg), but not significantly in moderate carbon tetrachloride-induced hepatic failure rabbits ($1.245{\pm}0.311$ L/hr/kg). The half-life(t1/2) of paclitaxel in severe carbon tetrachloride-induced hepatic failure rabbits ($7.71{\pm}2.16$ hr) was significantly (p<0.05) increased compared to that of normal rabbits ($5.75{\pm}1.44$hr), but not significantly in moderate carbon tetrachloride-induced hepatic failure rabbits ($6.77{\pm}1.76$hr). This results could be due to inhibition of paclitaxel metabolism in liver disorder rabbits since paclitaxel is essentially metabolized in liver. The findings suggest that the dosage regimen of paclitaxel should be adjusted when the drug would be administered in patients with liver disorder in a clinical situation.

• Biomolecules & Therapeutics
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• 제5권2호
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• pp.179-186
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• 1997

The pharmacokinetics and tissue distribution of DWP20373, a novel fluoroquinolone, were examined in rats and beagle dogs after a single intravenous and oral administration. Analysis of DWP20373 in plasma, tissue, and urine was performed by both HPLC and microbiological assay. The plasma drug concentration declined biexponentially both rats and beagle dogs. In the rats, the terminal drug elimination half-life (t$_{1}$2$\beta$/) was 64 min (IV) and 57 min (PO) by bioassay, and 76 min (IV) and 77 min (PO) by HPLC. Whereas in beagle dogs, t$_{1}$2$\beta$/ was 196 min (IV) and 350 min (PO). The volume of distribution at steady-state (Vd$_{ss}$ ) was 811 ml/kg (bioassay) and 2061 ml/kg (HPLC) in rats, and 2738 ml/kg (bioassay) in beagle dogs. The total body clearance (Cl$_{t}$) of DWP20373 was 10 ml/min/kg (bioassay) and 7 ml/min/kg (HPLC) in rats, and 11 m1/min/kg (bioassay) in beagle dogs. The extent of bioavailability after oral administration was 49% (bioassay) and 67% (HPLC) in rats, and 84% (bioassay) in beagle dogs. The 24-h urinary recovery, measured by bioassay, was 2.7% after oral dosing and 5.5% after intravenous dosing in rats. Serum protein binding ratio determined at 27g/ml was 78%. This drug was also distributed in tissues in the decreasing order of liver, kidney, spleen, lung, heart, and muscle determined at 30 min after oral administration.on.

• Biomolecules & Therapeutics
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• 제11권3호
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• pp.163-168
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• 2003

Pharmacokinetics of eupatilin (an active components of $Stillen^{\circledR}$, a new antigastritic agent) were investigated after both intravenous and oral administration at a dose of 30mg/kg to rats. After intravenous administration, the plasma concentrations of unchanged eupatilin declined rapidly with a mean terminal half-life of 0.101 h. Eupatilin was eliminated fast in rats; the total body clearance was 121 mL/min/kg. Eupatilin was mainly metabolized in rats; the percentage of intravenous dose of eupatilin excreted in 24 h urine and feces as unchanged eupatilin was only 2.5 and 0.919％, respectively. Eupatilin was mainly metabolized to form its glucuronide conjugate; after intravenous administration, 15.9 and 51.7％ of intravenous dose was excreted in 24 h urine and feces, respectively, as eupatilin plus its glucuronide. After oral administration, the absolute bioavailability was only 3.86％ based on $AUC_{0-24h}$ of eupatilin plus its glucuronide. Approximately 68.5％ of oral dose was not absorbed from the entire gastrointestinal tract. Therefore, it could be concluded that the superior effect of eupatilin in experimental animal models of gastric ulcer and inflammatory bowel disease after oral administration could be due to the local action of eupatilin. Further pharmacokinetic studies to elucidate the local action of eupatilin are required.

• 한국환경독성학회:학술대회논문집
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• 한국환경독성학회 2003년도 춘계학술대회
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• pp.189-189
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• 2003

Sophoricoside was isolated as the inhibitor of IL-5 bioactivity from Sophora japonica (Leguminosae). To develope as novel anti-allergic drug, kinetic study was performed in rats. Serum concentration of sophoricoside was measured by gas chromatography-mass spectrometry (GC/MS) in male Sprague-Dawley rat (250${\pm}$10g, n=5) after oral administration of sophoricoside (100mg/kg). The recovery of sophoricoside after extraction and concentration was above 95 % from rat serum. Between-day precision(relative standard deviation 2.2-2.8%) and within-day precision(2.0-12.1%) were determined from replicate analysis of a spiked control and incurred serum sample. The detection limits of sophoricoside in this serum was approximately 0.1 ng/mL. The Pharmacokinetic parameters were derived from the noncompartmental analysis. The C$\_$max/(3.56${\pm}$0.34 $\mu\textrm{g}$/mL) value for sophoricoside in male rat was observed at 7.6 h. The elimination half-life(t$\_$1/2/) of sophoricoside was approximately 4.47 h, the mean residence time (MRT) averaged 10.75 h, the total body clearance (Cl) averaged 0.0042 mL/min/kg. and the area under the serum concentration-time curve (AUC$\_$0-$\infty$/) was 24.93 $\mu\textrm{g}$$.$hr/mL.

• Journal of Pharmaceutical Investigation
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• 제36권1호
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• pp.19-22
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• 2006

The pharmacokinetics of nimodipine, following a single 16 mg/kg oral dose, was investigated in rabbits with hepatic failure induced by 0.5 mL/kg (mild), 1.0 mL/kg (moderate) and 2.0 mL/kg (severe) of carbon tetrachloride $(CCl_{4}$ : olive oil = 20 : 80, v/v). The plasma concentrations of nimodipine were determined by a high performance liquid chromatographic assay. The levels of sGOT and sGPT in rabbits with mild $(86.2{\pm}29.0\;and\;98.5{\pm}33.1\;unit/dL)$, moderate $(168.1{\pm}61.2\;and\;196.2{\pm}66.0\;unit/dL)$ and severe $(292.7{\pm}82.2\;and\;314.2{\pm}99.8\;unit/dL)$ hepatic failure were significantly increased compared to the control $(38.0{\pm}10.1\;and\;32.4{\pm}10.2\;unit/dL)$. The area under the plasma concentration-time curve (AUC) of nimodipine was significantly increased in mild $(131.7{\pm}28.1%)$, moderate $(168.8{\pm}32.8%)$ and severe $(204.6{\pm}58.3%)$ carbon tetrachloride-induced hepatic failure rabbits compared to the control (100%) rabbits. The volume of distribution $(V_{d})$ and the total body clearance $(CL_{t})$ of nimodipine were significantly decreased in all hepatic failure groups. The elimination rate constant $(K_{el})$ of nimodipine was significantly decreased in moderate and severe carbon tetrachloride-induced hepatic failure rabbits. There was a correlation between sGOT (y= 1.01x+241, r=0.993) or sGPT (y=0.92x +243, r=0.997) value and the AUC of nimodipine in the rabbits with hepatic failure. These findings suggest that the hepatic metabolism of nimodipine was inhibited by carbon tetrachloride-induced hepatic failure rabbits, resulting in the decrese in $V_{d}$ and $CL_{t}$ of nimodipine in the rabbits with mild, moderate and severe hepatic failure.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
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• pp.122-122
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• 1998

Propentofylline (PPF), a xanthine derivative, has been reported to be effective for the treatment of both vascular dementia and Alzheimer's disease. The elimination half-life of PPF was ranged from 15 to 45 min in rabbit and human, and PPF was rapidly disappeared from the blood. The objective of this experiment is to investigate whether xanthine analogues have effects on the profile of plasma concentration and metabolism of PPF. Caffeine (50 mg/kg, ip) was treated to Sprague-Dawley rats for consecutive 7 days and PPF was intravenously administered to rats 2 hr after the last dose of caffeine. In the other group, PPF was intravenously administered to rats 1 hr after a single dose of pentoxifylline (50 mg/kg, iv). Control group was treated with saline vehicle for the same period as in treatment groups. Blood was withdrawn at specific time intervals. PPF and one of its metabolite (POH) in plasma were determined by gas chromatography/nitrogen phosphorus detector. Plasma concentrations and pharmacokinetic parameters were compared between groups. The area under the curve (AUC) of PPF in rats treated sub chronically with caffeine was significantly decreased compared to control rats. Caffeine treatment results in a significant increase of total body clearance. The AUC of POH was significantly decreased in the caffeine-treated group. A single dose of pentoxifylline has no effect on the phramacokinetics of PPF. Reduction of the AUCs of PPF and POH both suggests that caffeine may increase the excretion of PPF with no affecting the metabolism of PPF to POH.