Identifying a long standing error in single-bolus determination of the hepatic extraction ratio for indocyanine green

2010 ◽  
Vol 111 (4) ◽  
pp. 641-646 ◽  
Author(s):  
Eugene H. Wissler
Keyword(s):  
Indocyanine Green ◽  
Extraction Ratio ◽  
Hepatic Extraction ◽  
Single Bolus ◽  
Hepatic Extraction Ratio

Clearance and Non-Invasive Determination of the Hepatic Extraction of Indocyanine Green in Baboons and Man

1983 ◽  
Vol 64 (2) ◽  
pp. 207-212 ◽  
Author(s):  
S. L. Grainger ◽  
P. W. N. Keeling ◽  
I. M. H. Brown ◽  
J. H. Marigold ◽  
R. P. H. Thompson
Keyword(s):  
Indocyanine Green ◽  
Accurate Determination ◽  
Liver Blood Flow ◽  
Compartment Model ◽  
Hepatic Extraction ◽  
Non Invasive ◽  
Two Compartment Model ◽  
Hepatic Extraction Ratio ◽  
Plasma Disappearance Curve

1. The disposition of an intravenous bolus of indocyanine green (ICG) has been studied in healthy man and baboons using a novel analysis of a two compartment pharmacokinetic model. 2. This analysis enabled the hepatic extraction ratio (ER) of dye to be determined solely from the plasma disappearance curve, and the ER determined did not differ from that measured by hepatic vein catheterization. 3. When compared with clearance measured at steady state, the two compartment model gave a significantly more accurate determination of plasma clearance than did the conventional one compartment model. 4. It is concluded that, in health, liver blood flow may be calculated accurately and noninvasively after a single intravenous injection of ICG.

Direct Measurement of Hepatic Extraction of Bile Acids in Subjects with and without Liver Disease

1981 ◽  
Vol 60 (1) ◽  
pp. 65-72 ◽  
Author(s):  
I. T. Gilmore ◽  
R. P. H. Thompson
Keyword(s):  
Liver Disease ◽  
Indocyanine Green ◽  
Bile Acids ◽  
Cholic Acid ◽  
Enterohepatic Circulation ◽  
Extraction Ratio ◽  
Constant Infusion ◽  
Hepatic Extraction ◽  
Glycocholic Acid ◽  
Hepatic Extraction Ratio

1. The hepatic extraction ratio of 14C-labelled bile acids has been measured directly by hepatic vein catheterization in five patients without liver disease (glycocholic acid, three; cholic acid, two) and in 16 patients with histologically confirmed liver disease (glycocholic acid, seven; cholic acid, nine). 2. After intravenous administration of [14C]-glycocholic acid by bolus injection (two control subjects) or constant infusion (one control subject), directly measured hepatic extraction ratio was 0.91, 0.84 and 0.88, greater than that for indocyanine green. The extraction ratio of [14C]cholic acid in two subjects was 0.72 and 0.70, confirming a lower extraction of the unconjugated bile acid. 3. The hepatic extraction ratio of both bile acids was reduced in patients with chronic liver disease (range 0.07–0.69), although the extraction ratio of glycocholic acid remained normal in one patient with viral hepatitis. 4. Estimates of liver flow calculated from the extraction of [14C]glycocholic acid, but not cholic acid, correlated with those calculated from indocyanine green kinetics, although numbers were small. 5. Measurement of the hepatic extraction of individual bile acids, not previously reported in man, allows a more accurate description of the enterohepatic circulation.

Estimation of the Hepatic Extraction Ratio of Indocyanine Green in Swine

1993 ◽  
Vol 84 (6) ◽  
pp. 681-685 ◽  
Author(s):  
David F. Kisor ◽  
Reginald F. Frye ◽  
Kenneth A. Kudsk
Keyword(s):  
Indocyanine Green ◽  
Pharmacokinetic Model ◽  
Original Model ◽  
Extraction Ratio ◽  
Hepatic Extraction ◽  
Glutathione S Transferase ◽  
Time Data ◽  
Model Estimate ◽  
New Model ◽  
Hepatic Extraction Ratio

1. The hepatic extraction ratio of Indocyanine Green was measured directly by trans-hepatic catheterization in 14 outbred swine (eight well-fed, six malnourished). A specific two-compartment pharmacokinetic model was fitted to the arterial Indocyanine Green concentration-time data and used to estimate the hepatic extraction ratio of Indocyanine Green. 2. The specific two-compartment pharmacokinetic model was modified to represent more accurately the physiological process of Indocyanine Green removal. Simulations were performed using this new model to estimate the hepatic extraction ratio of Indocyanine Green in the swine. 3. Similarly to previous findings, our data showed that the original model consistently overestimated the hepatic extraction ratio of Indocyanine Green (i.e. the model estimate was compared with the true, directly measured value). 4. The comparison of the modified model and the original model clearly indicates the reason for the overprediction of the hepatic extraction ratio of Indocyanine Green by the latter. The simulations using the new model indicate that the percentage of binding of Indocyanine Green to its transport protein (glutathione S-transferase) for removal in the bile will affect the estimation of the hepatic extraction ratio of Indocyanine Green. Thus, the amount of Indocyanine Green available for removal is less than that assumed by the original model.

Indocyanine Green elimination in patients with liver disease and in normal subjects

1991 ◽  
Vol 80 (2) ◽  
pp. 155-160 ◽  
Author(s):  
E. Burns ◽  
D. R. Triger ◽  
G. T. Tucker ◽  
N. D. S. Bax
Keyword(s):  
Indocyanine Green ◽  
Healthy Subjects ◽  
Time Course ◽  
Pharmacokinetic Model ◽  
Sampling Period ◽  
Extraction Ratio ◽  
Cirrhosis Of The Liver ◽  
Hepatic Extraction ◽  
Hepatic Extraction Ratio ◽  
Using Data

1. The validity of a two-compartment pharmacokinetic model for the estimation of the hepatic extraction ratio of Indocyanine Green was tested in six patients with cirrhosis of the liver. 2. No agreement was found between the value of the hepatic extraction ratio measured directly and that calculated using the two-compartment model. 3. To investigate the reasons for the failure of the model, an extended sampling period was used to define the time course of Indocyanine Green in plasma in six healthy subjects and in six patients with cirrhosis of the liver after a bolus injection of the dye. 4. Indocyanine Green was measurable in the plasma for up to 10 h after injection in healthy subjects, and up to 48 h after injection in the patients. The plasma elimination curve in both groups was best described by a triexponential function. 5. The clearance of Indocyanine Green calculated using data collected in the first 20 min after injection overestimated that calculated using data collected for as long as Indocyanine Green was measurable in the plasma. In the patients with cirrhosis the mean overestimate was 87%. 6. Thus, a two-compartment pharmacokinetic model was inappropriate for the description of the disposition of Indocyanine Green and estimates of the hepatic extraction ratio obtained using this model in patients with cirrhosis were inaccurate.

Total, renal and hepatic clearances of doxorubicin and formation clearance of doxorubicinol in patients with breast cancer: Estimation of doxorubicin hepatic extraction ratio

2020 ◽  
Vol 185 ◽  
pp. 113231 ◽  
Author(s):  
Leandro Francisco Pippa ◽  
Milena Locci de Oliveira ◽  
Adriana Rocha ◽  
Jurandyr Moreira de Andrade ◽  
Vera Lucia Lanchote
Keyword(s):  
Breast Cancer ◽  
Extraction Ratio ◽  
Hepatic Extraction ◽  
Hepatic Extraction Ratio

Quantitative aspects of insulin secretion and its hepatic and renal removal in sheep

1975 ◽  
Vol 229 (5) ◽  
pp. 1338-1343 ◽  
Author(s):  
RP Brockman ◽  
EN Bergman
Keyword(s):  
Insulin Secretion ◽  
Plasma Concentration ◽  
Extraction Ratio ◽  
Portal Blood ◽  
Hepatic Extraction ◽  
Plasma Flows ◽  
Secretory Rate ◽  
Physiological Limits ◽  
Hepatic Extraction Ratio

The secretion of insulin into the portal blood and its removal by the liver and kidneys in conscious fed sheep were determined by simultaneously measuring venoarterial plasma concentration differences and portal, hepatic, and renal plasma flows. The basal secretory rate of insulin was 0.43 +/- 0.03 U/h or 7.8 mU/kg-h. The secretory rate of insulin and the amount of insulin presented to the liver also were altered by 2-h intraportal infusions of glucagon (150 mug/h), insulin (1.17 U/h), and insulin (1.17 U/h) lus glucose (2.2 g/h). Hepatic removal under all conditions was about 50% of the insulin secretory rate, although the extraction ratio was only 0.08. Renal removal was 35% of the insulin secretory rate. The renal extraction ratio was 0.35. During insulin-induced hypoglycemia and also during starvation, the hepatic extraction ratio of insulin increased significantly, but the removal as a percentage of insulin secretion did not change. It appears that in sheep on a maintenance diet the basal secretory rate of insulin is less than that of nonruminant species and that, within physiological limits, the liver disposes of about one-half and the kidney about one-third of the insulin. Other tissues, presumably, remove the remaining 10--20%.

Variation in Hepatic Extraction Ratio with Unbound Drug Fraction: Discrimination Between Models of Hepatic Drug Elimination

1985 ◽  
Vol 74 (2) ◽  
pp. 205-207 ◽  
Author(s):  
Amanda J. Byrne ◽  
Denis J. Morgan ◽  
Paul M. Harrison ◽  
Allan J. McLean
Keyword(s):  
Extraction Ratio ◽  
Drug Elimination ◽  
Hepatic Extraction ◽  
Hepatic Drug ◽  
Hepatic Extraction Ratio

Ca2+ concentration influences the hepatic extraction of bioactive human PTH-(1-34) in rats

1989 ◽  
Vol 256 (1) ◽  
pp. E87-E92
Author(s):  
P. D'Amour ◽  
P. M. Huet
Keyword(s):  
Liver Perfusion ◽  
Extraction Ratio ◽  
Hepatic Veins ◽  
Gel Chromatography ◽  
Hepatic Extraction ◽  
Rat Liver Perfusion ◽  
Chromatography Analysis ◽  
System A ◽  
Hepatic Extraction Ratio

The regulation of bioactive human parathyroid hormone [hPTH-(1-34)] hepatic extraction was studied in vitro by means of an isolated rat liver perfusion system. A standard buffer containing 20% red blood cells, 2% albumin, and variable concentrations of hPTH-(1-34) and Ca2+ was used in nonrecirculation experiments. Hepatic blood flow was kept constant at approximately 1.8 ml.g liver-1.min-1. hPTH in portal and hepatic veins was measured by a radioimmunoassay specific for hPTH-(1-34), and the results obtained were validated by gel chromatography analysis of the hormone measured. Results are expressed as mean +/- SD of five to six different experiments. In normocalcemic conditions (Ca2+ approximately 1.2 mmol/l), the hepatic extraction ratio of hPTH remained stable at 0.357 +/- 0.011 and 0.370 +/- 0.010 for hPTH-(1-34) concentrations of 0.156 +/- 0.002 and 1.314 +/- 0.014 pmol/ml; it decreased to 0.145 +/- 0.013 (P less than 0.001) for a hPTH-(1-34) concentration of 5.817 +/- 0.167 pmol/ml. Kinetics analysis of the normocalcemic data disclosed a Vmax of 1.971 +/- 0.18 pmol.min-1.g liver-1 and a Km of 1.410 +/- 0.39 pmol/ml. When hPTH-(1-34) concentration was kept stable with varying Ca2+ concentrations, elevated (1.62 +/- 0.01 mmol/l) Ca2+ gave an hepatic extraction ratio similar to normocalcemic conditions (0.335 +/- 0.014 vs. 0.357 +/- 0.011 mmol/l), whereas it significantly decreased in hypocalcemia (0.78 +/- 0.01 mmol/l) to 0.219 +/- 0.014 mmol/l (P less than 0.001). Kinetics were similar to normocalcemic conditions when Ca2+ concentration was elevated but appeared modified by hypocalcemia.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Considering Age Variation When Coining Drugs as High versus Low Hepatic Extraction Ratio

2016 ◽  
Vol 44 (7) ◽  
pp. 1099-1102 ◽  
Author(s):  
F. Salem ◽  
K. Abduljalil ◽  
Y. Kamiyama ◽  
A. Rostami-Hodjegan
Keyword(s):  
Extraction Ratio ◽  
Hepatic Extraction ◽  
Hepatic Extraction Ratio ◽  
Age Variation
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