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.

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.

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

Radiolabelled Bile Acid Clearance in Control Subjects and Patients with Liver Disease

1979 ◽  
Vol 57 (6) ◽  
pp. 499-508 ◽  
Author(s):  
L. R. Engelking ◽  
S. Barnes ◽  
C. A. Dasher ◽  
D. C. Naftel ◽  
B. I. Hirschowitz
Keyword(s):  
Liver Disease ◽  
Bile Acid ◽  
Cholic Acid ◽  
Indirect Evidence ◽  
Normal Subjects ◽  
Serum Bile Acid ◽  
Tracer Injection ◽  
Bile Acid Concentration ◽  
Glycocholic Acid ◽  
Acid Clearance

1. The serum bile acid disappearances of tracer doses of [24-14C]cholic acid and [1-14C]-glycocholic acid were studied in eight normal subjects and 11 patients with chronic liver disease (with or without cholestasis) in order to determine the effect of liver disease on hepatic clearances, reflux of conjugated cholic acid and initial distribution volume of each tracer. 2. Total cholic acid clearance was significantly reduced from normal (7·2 ± 0·7 ml min−1 kg−1, mean ± se) in patients with liver disease (69–88%, group means) as were unconjugated cholic acid (51–68%) and glycocholic acid (66–83%) clearance. 3. Extensive regurgitation of labelled conjugated cholic acid (after unconjugated cholic acid tracer injection) among cholestatic patients accounted for 69 ± 5% of total 14C remaining in serum at 70 min, thus masking a less-impaired uptake process. 4. The hepatic extraction efficiency for conjugated cholic acid among controls (86 ± 8%) was greater than that for unconjugated cholic acid (60 ± 4%), and was greatly reduced among patients (7–27%, group means). 5. Normal subjects and patients with cirrhosis without cholestasis did not distribute the isotope to extravascular, extrahepatic spaces, in contrast to cholestatic patients with serum bile acid concentration > 149μmol/l. 6. Careful evaluation of serum disappearance of bile acids as well as chromatographic separation of regurgitated metabolites, could provide investigators with indirect evidence of defects in the rate-limiting steps (uptake, conjugation or excretion) of hepatic bile acid transport.

scholarly journals Bile salts of the green turtle Chelonia mydas (L.)

1978 ◽  
Vol 171 (2) ◽  
pp. 409-412 ◽  
Author(s):  
G A D Haslewood ◽  
S Ikawa ◽  
L Tökés ◽  
D Wong
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Cholic Acid ◽  
Green Turtle ◽  
Bile Salts ◽  
Deoxycholic Acid ◽  
Enterohepatic Circulation ◽  
Chelonia Mydas ◽  
Independent Evolution ◽  
Alpha 7

1. Bile salts of the green turtle Chelonia mydas (L.) were analysed as completely as possible. 2. They consist of taurine conjugates of 3 alpha, 7 alpha, 12 alpha, 22 xi-tetrahydroxy-5 beta-cholestan-26-oic acid (tetrahydroxysterocholanic acid) and 3 alpha 12 alpha, 22 xi-trihydroxy-5 beta-cholestan-26-oic acid, with minor amounts of 3 alpha, 7 alpha, 12 alpha-trihydroxy-5beta-cholan-24-oic acid (cholic acid), 3alpha, 12 alpha-dihydroxy-5beta-cholan-24-oic acid (deoxycholic acid) and possibly other bile acids. 3. Cholic acid and deoxycholic acid represent the first known examples of bile acids common to chelonians and other animal forms: they may indicate independent evolution in chelonians to C24 bile acids. 4. The discovery of a 7-deoxy C27 bile acid is the first evidence that C27 bile acids or their conjugates have an enterohepatic circulation.

Effects of a Meal on Plasma Clearance of [14C]Glycocholic Acid and Indocyanine Green in Man

1981 ◽  
Vol 61 (3) ◽  
pp. 325-330 ◽  
Author(s):  
J. H. Marigold ◽  
I. T. Gilmore ◽  
R. P. H. Thompson
Keyword(s):  
Indocyanine Green ◽  
Plasma Clearance ◽  
Enterohepatic Circulation ◽  
Liver Blood Flow ◽  
Normal Subjects ◽  
Volume Of Distribution ◽  
Blue Dye ◽  
Glycocholic Acid ◽  
Disappearance Curve ◽  
Plasma Disappearance Curve

1. The fasting plasma disappearance curve of [14C]glycocholic acid after intravenous injection was compared in nine normal subjects with that obtained 100 min after a standard liquid test meal. 2. Plasma disappearance curves of indocyanine green were determined in 13 normal subjects under the same conditions. 3. Plasma clearances were significantly increased after the meal for both [14C]glycocholic acid (median 455 ml min−1 m−2, range 376–672 increased to 704, 528–1968; P < 0.01) and indocyanine green (359, 227–473 increased to 435, 358–985; P < 0.01). 4. Median initial volume of distribution was unaltered, but in four subjects it was greatly increased after the meal, although no alteration in plasma volume, measured with Evans blue dye, was observed. 5. The increased postprandial plasma clearance of glycocholic acid is probably due to an increase in liver blood flow, and suggests that in health this part of the enterohepatic circulation of bile acids also varies with meals.

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%.

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