Pharmacokinetics of Indocyanine Green in Rats with Experimentally Induced Hepatic Diseases.

Kimura, Takeshi; Nakayama, Shuko; Yamao, Tadanao; Kurosaki, Yuji; Nakayama, Tomohiro

doi:10.1248/bpb.16.1140

Cited by 16 publications

(24 citation statements)

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“…ICG was chosen due to its known pharmacokinetics [11][12][13] and its established use in the clinical setting. ICG handling by the liver is predicted from its plasma disappearance curve and represents a widely used method for liver function testing in acute and chronic hepatic disorders [14].…”

Section: Discussionmentioning

confidence: 99%

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In vivo imaging of hepatic excretory function in the rat by fluorescence microscopy

Recknagel

Claus

Neugebauer

et al. 2012

Journal of Biophotonics

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Applying intravital fluorescence microscopy, we assessed sinusoidal delivery and biliary clearance of two different polymethine dyes. DY635, a benzopyrylium‐based hemocyanine dye with shorter excitation wavelength than indocyanine green (ICG), was validated for assessment of hepatic excretory function. Decrease of DY635 and ICG reflecting transcellular transport was 83 ± 4% (DY635) and 14 ± 2% (ICG; p < 0.05) over 35 minutes, respectively. In cholestasis, hepatobiliary excretion of DY635 was markedly impaired (control 3176 ± 148 pmol vs. cholestatic 1929 ± 179 pmol; p < 0.05). DY635 even enabled an analysis at high resolution suggesting 1.) hepatocyte uncoupling and 2.) failure of primarily the canalicular pole, allowing in vivo insights into molecular mechanisms of this critical facet of hepatobiliary function. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)

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Section: Discussionmentioning

confidence: 99%

“…It is widely applied in medical diagnostics. Due to its solely hepatobiliary excretion [12,13], assessment of the clearance of this dye from bloodstream is applied in the clinical setting for assessment of excretory liver function reflecting both the microcirculation and hepatic (cell) function [14].…”

Section: Dyes For Analysis Of Hepatic Excretory Functionmentioning

confidence: 99%

In vivo imaging of hepatic excretory function in the rat by fluorescence microscopy

Recknagel

Claus

Neugebauer

et al. 2012

Journal of Biophotonics

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“…After application of CCl 4 to the rat liver surface, liver and kidney function were evaluated by monitoring several biochemical parameters. In addition, hepatic and renal lipid peroxidation levels induced by liver surface application of CCl 4 were compared with those in rats treated orally or intraperitoneally.…”

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confidence: 99%

A Novel Method for Preparation of Animal Models of Liver Damage: Liver Targeting of Carbon Tetrachloride in Rats.

Mukai

Mera

Nishida

et al. 2002

Biological & Pharmaceutical Bulletin

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Animal models prepared by treatment with toxic compounds such as a carbon tetrachloride have been used to examine drug disposition in hepatic diseases. However, it is possible that these compounds accumulate and cause damage to other organs as they are administered systemically. In this study, we used the liver surface application technique to deliver a toxic compound to the liver to prepare an appropriate animal model in which only the liver is significantly damaged. To restrict the absorption area in the liver, a cylindrical diffusion cell was attached to the liver surface of male Wistar rats. Twenty-four hours after direct addition of carbon tetrachloride to the diffusion cell, plasma levels of glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT), and hepatic malondialdehyde (MDA) concentration were increased, while there were no changes in plasma creatinine or renal MDA level. On the other hand, not only GOT, GPT and hepatic MDA, but also creatinine and renal MDA levels were markedly increased by p.o. and i.p. administration of carbon tetrachloride, suggesting renal damage. These results indicated that the animal models of liver damage prepared by utilizing drug delivery techniques to accumulate toxic compounds in the liver would enable us to investigate the precise effects of hepatic disorder on drug disposition.

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“…In fact, more than 80% of the intravenous dose of the drug is recovered in the bile as parent and metabolite forms, whereas the recovery in urine is limited (i.e., 10% of the dose) (5,6). Liver diseases likely affect the pharmacokinetics of drugs that are mainly metabolized or excreted in the liver (7,8). To study the pharmacokinetics of drugs in hepatic disease, an experimental hepatic injury (EHI) induced by a single dose of carbon tetrachloride (CCl 4 ) is a widely used model of hepatic disease (9,10).…”

Section: Introductionmentioning

confidence: 99%

Altered Pharmacokinetics of Daunorubicin in Rats with CCl4-Induced Hepatic Injury

et al. 2007

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-PURPOSE. The effect of CCl 4 -induced experimental hepatic injury (CCl 4 -EHI) on the pharmacokinetics of daunorubicin was investigated systemically in rats, in an attempt to elucidate the major determinants of the effect of CCl 4 -EHI on the pharmacokinetics of the drug. METHODS. CCl 4 -EHI was induced in rats by a single intraperitoneal injection of CCl 4 (1mL/kg rat), and a 24 h fasting period. Daunorubicin was administered intravenously to control and EHI rats at a dose of 11.3 mg/mL/kg and the in vivo pharmacokinetics was studied. The in vitro uptake of the drug into isolated hepatocytes and canalicular liver plasma membrane (cLPM) vesicles, as well as the liver microsomal degradation of the drug, were also determined. RESULTS. The area under the plasma concentration-time curve (AUC) of daunorubicin was increased by 1.6 times, resulting in a 34% decrease in the systemic clearance (CL) in rats with CCl 4 -EHI. The apparent biliary (CL bile ) and urinary (CL urine ) clearance of the drug were unchanged, whereas the AUC of daunorubicinol, the major metabolite of daunorubicin, was decreased by 66% in rats with CCl 4 -EHI. EHI seemed to affect the hepatobiliary elimination of the drug in several ways: the in vitro intrinsic sinusoidal uptake clearance was decreased by 20%; the in vitro intrinsic canalicular excretion clearance of the drug was increased by 1.7 times; and the in vitro liver microsomal degradation of daunorubicin was significantly retarded. CONCLUSIONS. CCl 4 -EHI appears to impair the hepatic metabolism of daunorubicin, thereby decreasing the CL and increasing the AUC of daunorubicin.

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Pharmacokinetics of Indocyanine Green in Rats with Experimentally Induced Hepatic Diseases.

Cited by 16 publications

References 0 publications

In vivo imaging of hepatic excretory function in the rat by fluorescence microscopy

In vivo imaging of hepatic excretory function in the rat by fluorescence microscopy

A Novel Method for Preparation of Animal Models of Liver Damage: Liver Targeting of Carbon Tetrachloride in Rats.

Altered Pharmacokinetics of Daunorubicin in Rats with CCl4-Induced Hepatic Injury

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