• Title/Summary/Keyword: Hepatic uptake

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Pharmacokinetic Modeling and Simulation of the Carrier-Mediated Hepatic Transport of Organic Anions (음이온계 약물의 간수송과정에 있어서 담체매개 수송의 약물동력학적 모델링 및 시뮬레이션)

  • 이준섭;강민희;김묘경;이명구;정석재;심창구;정연복
    • YAKHAK HOEJI
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    • v.47 no.2
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    • pp.110-119
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    • 2003
  • The purpose of the present study was to kinetically investigate the carrier-mediated uptake in the hepatic transport of organic anions, and to simulate the ″in vivo counter-transport″ phenomena, using kinetic model which was developed in this study. The condition that the mobility of carrier-ligand complex is greater than that of free carrier is not essential for the occurrence of ″counter-transport″ phenomenon. To examine the inhibitory effects on the initial uptake of a ligand by the liver, it is necessary to judge whether the true counter-transport mechanism (trans-stimulation) is working or not. The initial plasma disappearance curves of a organic anion were then kinetically analyzed based on a flow model, in which the ligand is eliminated only from the peripheral compartment (liver compartment). Moreover, ″in vive counter-transport″ phenomena were simulated based on the perfusion model which incorporated the carrier-mediated transport and the saturable intracellular binding. The ″in vivo counter-transport″ phenomena in the hepatic transport of a organic anion were well demonstrated by incorporating the carrier-mediated process. However, the ″in vivo counter-transport″ phenomena may be also explained by the enhancement of back diffusion due to the displacement of intracellular binding. In conclusion, one should be more cautious in interpreting data obtained from so-called ″in vivo counter-transport″ experiments.

Estimation of the Arterial Fraction of Total Hepatic Flow from Radionuclide Angiogram Using $^{99m}Tc-DISIDA$ ($^{99m}Tc-DISIDA$를 이용한 간 혈류 중 동맥 분획의 측정)

  • Lee, Hae-Giu;Lim, Gye-Yeon;Yang, Il-Kwon;Kim, Hack-Hee;Lim, Jung-Ik;Bahk, Yong-Whee;Han, Sok-Won;Han, Nam-Ik;Lee, Young-Sok
    • The Korean Journal of Nuclear Medicine
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    • v.25 no.2
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    • pp.200-206
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    • 1991
  • Arterial fraction of total hepatic blood flow was estimated by a new method, slope method, on radionuclid angiogram using $^{99m}Tc-DISIDA$ and was compared with that from $^{99m}Tc-Phytate$ radionuclide angiogram. This study included 11 of normal subjects, 37 of intermediate group with various liver diseases, and 25 patients with liver cirrhosis. We analyzed the datas with slope method from radionuclide angiograms and the results were compared with hepatic arterial fractions from uptake method, introduced by Lee et al. at 1986. The hepatic arterial fractions from radionuclide angiograms using $^{99m}Tc-DISIDA$ and $^{99m}Tc-Phytate$ were $0.32{\pm}0.09\;and\;0.31{\pm}0.11$ respectively in normal subjects, and $0.75{\pm}0.18\;and\;0.77{\pm}0.21$ respectively in patients with liver cirrhosis. The hepatic arterial fractions by the slope method was well correlated with those of the uptake method on $^{99m}Tc-DISIDA$ scan. There was high correlation between the hepatic arterial fractions from $^{99m}Tc-DISIDA$ and $^{99m}Tc-Phytate$ scans. Hepatic arterial fraction estimated by the slope method is a useful index for the diagnosis of liver cirrhosis and the evaluation of status of portal hypertension.

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A Clinical Study on the Value of a Scoring System of the Scanning Images in Liver Cirrhosis (간경변증(肝硬變症)의 간주사상판독(肝走査像判讀)에 있어서의 평점제적용(評點制適用)에 관(關)한 임상적(臨床的) 연구(硏究))

  • Chang, Ko-Chang
    • The Korean Journal of Nuclear Medicine
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    • v.4 no.2
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    • pp.41-53
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    • 1970
  • Although the radioisotope liver scan has primarily been of use in the detection of the intra-hepatic space occupying lesions, there has been an increasing awareness of its use in evaluation of liver function. In this study, the degree of hepatomegaly, changes in shape and mottling radiodensity on each lobe and splenic visualization in the liver scans done with colloidal radiogold were numerically expressed as scores under the arbitrary standard in 210 patients with liver cirrhosis. The clinical value of this scoring system was studied with special regards to the correlation between the radiogold hepatic uptake half time and conventional liver function tests. Following were the results; 1) The normal scan appeared in 6.7% of 210 patients with liver cirrhosis. 2) The colloidal radiogold hepatic uptake half time was abnormally and progressively prolonged in parallel to severity of hepatocellular dysfunction. The mean hepatic uptake half time in cirrhosis showing normal scan was $2.76{\pm}0.73$ minutes. 3) The scoring system was well correlated with the serum albumin and globulin levels, A/G ratio and BSP retention. There was some correlative tendency in alkaline phosphatase activity. 4) There was no correlation with the thymol turbidity test, cholesterol levels, transaminase activities and bilirubin levels. 5) The spleen was visualized in 38.6% of total patients with liver cirrhosis. Excluding normal scans in liver cirrhosis, the spleen was visualized in 41.3%. 6) The scoring system appears to confirm the clinical diagnosis and to give a reliable estimate of the degree of hepatocellular dysfunction in patients with liver cirrhosis.

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Diffuse Hepatic Uptake of $^{99m}Tc$-DPD on Whole Body Bone Scan: The Influence of MRI Contrast (전신 뼈 검사에서 $^{99m}Tc$-DPD의 미만성 간 섭취: MRI 조영제의 영향)

  • Yun, Jong Jun;Jeong, Ji Uk;Hwang, Ju Won
    • The Korean Journal of Nuclear Medicine Technology
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    • v.16 no.2
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    • pp.57-61
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    • 2012
  • Purpose : The whole body bone scan on nuclear medicine is a widely accepted examination and procedure. However, unusual nonosseous uptake can be observed, which reflects a rare interaction between the radiopharmacceutical and the patient. This study aimed to evaluate the influence of MRI(Magnetic Resonance Imaging) contrast and $^{99m}Tc$-DPD(Dicarboxpropane diphosphonate) on whole body bone scan. Materials and Methods : We analyzed the 982 patients who were examined by $^{99m}Tc$-DPD on whole body bone scan in nuclear medicine department of pusan national university hospital from january to december 2010. All these 982 patients had MRI contrast administration prior to whole body bone scan. We analyzed laboratory test. Results : 46 patients(men 39, women 7) showed diffuse hepatic uptake on whole body bone scan. These uptakes were disappeared on the follow-up whole body bone scan. There were no significant difference of CBC test, liver function tests and renal function tests. Conclusion : The study might be an indirect evidence that diffuse hepatic and splenic uptake of 99mTc-DPD on whole body bone scan after intravenous administration of Gadolinium(Gd) MRI contrast. To perform a precise examination, Gd-contrast agent should be removed from the body before performing a whole body bone scan.

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Effect of Cimetidine on the Hepatic Blood flow -On the Basis of Pharmacokinetics of Indocvanine Green in Rats- (시메티딘이 간혈류량에 미치는 영향 - Rat에 있어서 Indocyanine Green의 체내 동태를 중심으로 -)

  • Lee, Yong-Bok;Koh, Ik-Bae
    • Korean Journal of Clinical Pharmacy
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    • v.3 no.2
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    • pp.163-168
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    • 1993
  • The influence of cimetidine pretreatment(100mg/kg, single i.p.) on the hepatic blood flow was investigated using pharmacokinetic parameters of indocyanine green(ICG) in the rat on the basis of hepacc perfusion-limited model. ICG(1mg/kg) was respectively administered via femoral and portal vein to the control and to the cimetidine-pretreated rats. The rate constant K12, K20 and the systemic clearance(CLt) of ICG were significantly(p<0.05) decreased ill the cimetidine-pretrea-to(B rats, but no significant diffirences were observed in hematocrit and liver weight. The biliary excretion rates of ICG were also decreased regardless of the route of administration in the cimetidine-pretreated rats. And also the hepatic blood flow in rats was decreased about $16\%$ by cimetidine. It may be concluded that the decreased hepatic blood flow with cimetidine mainly contributed to the decreased hepatic uptake and the decreased systemic clearance of ICG.

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Kinetic Analysis of the Hepatic Uptake and Biliary Excretion of IH-901. a Potential Anticancer Agents. in Rats

  • Lee, Pung-Sok;Sung, Jong-Hwan;Chung, Youn-Bok
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.422.2-423
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    • 2002
  • The purpose of the present study was to investigate the hepatic uptake and biliary excretion of IH-901. a potential anticancer agents. in rats. IH-901 was mainly distributed into the liver after its iv administration at the dose of 10-30 mg/kg. The liver concentration of IH-901 at 7 min after its Iv administration was comparable with its initial concentration of the plasma. Moreover. recovery ratio of IH-901 in the bile for 6 hr was more than 40% after its iv administration. (omitted)

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T1-201 Per Rectum Scintigraphy in Chronic Liver Disease: Assessment of T1-201 Uptake Indices (만성 간질환에서의 T1-201 경직장 문맥 신티그라피: T1-201 섭취 지표의 평가)

  • Moon, Won-Jin;Choi, Yun-Young;Cho, Suk-Shin;Lee, Min-Ho
    • The Korean Journal of Nuclear Medicine
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    • v.33 no.1
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    • pp.49-56
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    • 1999
  • Purpose: Heart to liver ratio on T1-201 per rectal scintigraphy (shunt index) is known to be useful in the assessment of portal systemic shunt. We assessed T1-201 uptake pattern and early liver/heart uptake rate of T1-201 and correlated with shunt index in patients with chronic active hepatitis (CAH) and liver cirrhosis (LC). Materials and Methods: Fifty eight patients with biopsy-proven chronic liver disease (35 with CAH, 23 with LC) underwent T1-201 per rectum scintigraphy after instillation of 18.5 MBq of T1-201 into the upper rectum. We evaluated hepatic uptake (type 1 : homogeneous, 2: inhomogeneous segmental, 3: inhomogeneous nonsegmental) and extrahepatic uptake of spleen, heart and kidney (grade 0: no uptake, 1: less than liver, 2: equal to liver, 3: greater than liver). We measured the early liver/heart uptake rate (the slope of the liver to heart uptake ratio for 10 min) and shunt index (heart to liver uptake ratio). T1-201 uptake pattern and early liver/heart uptake rate of T1-201 was correlated with the pathologic diagnosis and shunt index. Results: Hepatic uptake patterns of type 1 and 2 were dominant in CAH (CAH: 27/35, LC. 8/23), and type 3 in LC (CAH: 8/35, LC: 15/23)(p<0.005). The grades of extrahepatic uptake were higher in LC than in CAH (spleen: p<0.001, other soft tissue: p<0.005). The early liver/heart uptake rate of CAH ($0.110{\pm}0.111$) was significantly higher than that of LC ($0.014{\pm}0.090$)(p<0.001). The sensitivity and specificity of the early liver/heart uptake rate were 77.7% and 67.7% in differentiating LC from CAH. There was negative correlation between early liver/heart uptake rate and shunt index (r=-0.3347, p<0.01). Conclusion: Hepatic and extrahepatic uptake pattern and early liver/heart uptake rate on T1-201 per rectum scintigraphy are useful in the assessment of portal systemic shunt in patients with chronic liver disease.

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Altered Biodistribution of Gallium-67 in a Patient with Multiple Factors Influencing Iron-transport Protein Saturation (철운반단백질 포화정도에 따른 Gallium-67 체내분포의 변화: 증례보고)

  • Choi, Joon Young;Kim, Sang Eun;Lee, Kyung Han;Kim, Byung-Tae
    • The Korean Journal of Nuclear Medicine
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    • v.32 no.1
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    • pp.114-119
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    • 1998
  • We present a case of a young female patient with fulminant hepatitis who showed an altered biodistribution of Ga-67, after being scanned twice at 10 month intervals. On initial scan, uplake of Ga-67 was increased in the liver, kidneys, and skeletons. Increased hepatic Ga-67 uptake may be explained by increased transferrin unbound Ga-67 that was taken up by the inflamed liver. The saturation of iron-binding proteins due to multiple transfusions may lead to increased renal and skeletal Ga-67 uptake. On follow-up scan hepatic Ga-67 uptake was markedly increased. Also increased Ga-67 uptake in the axial skeleton and normalized renal uptake were shown. The findings were consistent with iron deficiency anemia. This case demonstrates altered Ga-67 biodistribution associated with multiple transfusions, fulminant hepatitis, and iron deficiency anemia.

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Kinetic Analysis of the Counter-transport Phenomenon in the Hepatic Transport of Organic Anionic Drugs (유기 음이온계 약물의 간수송과정에 있어서 대향수송현상에 관한 속도론적 연구)

  • Chung, Youn-Bok;Han, Kun;No, Jung-Ryul
    • Journal of Pharmaceutical Investigation
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    • v.22 no.4
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    • pp.289-300
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    • 1992
  • The counter-transport phenomena in the hepatic transport of 1-anilino-8-naphthalene sulfonate (ANS) were kinetically investigated by analyzing the plasma disappearance-time profiles and the transport into the isolated hepatocytes. In vivo "counter transport phenomena" were simulated based on the perfusion model which incorporated the carrier-mediated transport and the saturable intracellular binding. The condition that the mobility of carrier-ligand complex is greater than that of free carrier is not essential for the occurrence of counter-transport phenomenon. To examine the inhibitory effects on the initial uptake of a ligand by the liver, it is necessary to judge whether the true counter-transport mechanism (trans-stimulation) is working or not. The initial plasma disappearance curves of ANS were then kinetically analyzed based on a two-compartment model, in which the ligand is eliminated only from the peripheral compartment (liver compartment). No effects on the initial plasma disappearance rates of ANS were observed after preloading of bromophenol blue (BPB) or rose bengal (RB) in the liver. Inhibitory effect of BPB or RB on the initial uptake (or efflux) rates of ANS by the isolated hepatocytes were not observed, suggesting that the true counter transport mechanism is not working. In conclusion, checking the preloading effects of transstimulation on the initial uptake of a ligand by the liver could be a useful criterion for carrier cycling and common use of the same carrier between two ligands. However, one cannot exclude those possibilities even if the preloading effects cannot be observed.

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Hepatic Uptake and Stability of Acyclovir-Asialofetuin Conjugate (아시클로버-아시알로페투인 접합체의 간 포획 및 안정성)

  • Son, Sung-Ho;Huh, Keun;Lee, Young-Dae;Oh, Doo-Man;Yong, Chul-Soon
    • Journal of Pharmaceutical Investigation
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    • v.27 no.1
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    • pp.1-10
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    • 1997
  • For the purpose of improving the chemotherapeutic index of acyclovir(ACV), it was conjugated with asialofetuin(AF), which has been reported to enter into hepatocytes. When $[H^3]$ acyclovir in itself or its conjugate were administered to rats, the latter was taken up more selectively by the liver than any other tissues. The stability of ACVMP-AF conjugate in phosphate buffer (pH 5.0) and rat liver homogenate showed a pseudo-first order profile. ACVMP-AF, however, was relatively stable in pH7.4 phosphate buffer and rat plasma. The conjugate was added to the isolated rat hepatocyte and cellular uptake was monitored by scintillation counting for up to 6 hours at $37^{\circ}C$. Hepatocytes incubated with the conjugate exhibited radioactivities significantly enhanced over control levels dose-dependently, i.e., a 3-40 fold increase in radioactivities was observed over controls at the conjugate concentrations of $0.1-10\;{\mu}g/ml$. The AUQ in the liver, kidney, spleen, intestine and lung was higher in treatment with ACVMP-AF than that in treatment with ACV. In treatment with ACVMP-AF, the weighted-average overall drug targeting efficiency(Te) for the liver was higher than in treatment with ACV(57.00 vs 13.31 %), and the weighted-average tissue exposure(Re) was 5.03 for the liver. These results indicated that ACVMP-AF conjugate was rapidly taken up by hepatocytes and could be an efficient and selective hepatic targeting system.

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