A dispersion model of hepatic elimination: 2. Steady-state considerations-influence of hepatic blood flow, binding within blood, and hepatocellular enzyme activity

1986 ◽  
Vol 14 (3) ◽  
pp. 261-288 ◽  
Author(s):  
Michael S. Roberts ◽  
Malcolm Rowland
Keyword(s):  
Blood Flow ◽  
Enzyme Activity ◽  
Steady State ◽  
Hepatic Blood Flow ◽  
Dispersion Model ◽  
Hepatic Elimination

Effect of enteral versus parenteral feeding on hepatic blood flow and steady state propofol pharmacokinetics in ICU patients

1998 ◽  
Vol 24 (8) ◽  
pp. 795-800 ◽  
Author(s):  
N. Van Brandt ◽  
P. Hantson ◽  
Y. Horsmans ◽  
P. Mahieu ◽  
R. K. Verbeeck
Keyword(s):  
Blood Flow ◽  
Steady State ◽  
Hepatic Blood Flow ◽  
Parenteral Feeding ◽  
Icu Patients

Effects of liver blood flow on hepatic uptake kinetics of galactose in anesthetized cats: parallel tube model

1987 ◽  
Vol 65 (6) ◽  
pp. 1193-1199 ◽  
Author(s):  
C. V. Greenway ◽  
F. J. Burczynski
Keyword(s):  
Blood Flow ◽  
Steady State ◽  
Hepatic Blood Flow ◽  
Venous Blood ◽  
Liver Blood Flow ◽  
Control Flow ◽  
Tube Model ◽  
Blood Flows ◽  
Parallel Tube ◽  
Parallel Tube Model

Hepatic galactose uptake in cats anesthetized with pentobarbital was determined during (i) steady-state infusions at several doses, (ii) rapidly increasing infusion rates at different blood flows, and (iii) prolonged infusion of a single dose at different blood flows. The hepatic venous long-circuit technique was used to allow frequent sampling of arterial, portal, and hepatic venous blood without depletion of the animal's blood volume and to allow measurement and alteration of total hepatic blood flow. Uptake was shown to follow Michaelis–Menten kinetics and was consistent with the "parallel tube model." The kinetic parameters Vmax and Kmax could be determined under steady-state and nonsteady-state conditions and were independent of hepatic blood flow over the range 60–150% of control flow. Mean Vmax was 80 μmol/(min∙100 g liver) and mean Km was 215 μM. Vmax declined by 50% when flow was reduced to half normal. It is concluded that the parallel tube model can be used to describe and predict hepatic galactose kinetics in anesthetized cats, although other models may fit the data equally well.

scholarly journals Roles of hepatic blood flow and enzyme activity in the kinetics of propranolol and sotalol.

1980 ◽  
Vol 9 (4) ◽  
pp. 399-405 ◽  
Author(s):  
HI Pirttiaho ◽  
EA Sotaniemi ◽  
RO Pelkonen ◽  
U Pitkanen ◽  
M Anttila ◽  
...  
Keyword(s):  
Blood Flow ◽  
Enzyme Activity ◽  
Hepatic Blood Flow ◽  
Kinetics Of

Halothane-induced liver injury in guinea-pigs: Importance of cytochrome P450 enzyme activity and hepatic blood flow

1996 ◽  
Vol 11 (6) ◽  
pp. 594-601 ◽  
Author(s):  
GEOFFREY C. FARRELL ◽  
LINDA FROST ◽  
MICHAEL TAPNER ◽  
JACQUELINE FIELD ◽  
MARTIN WELTMAN ◽  
...  
Keyword(s):  
Blood Flow ◽  
Enzyme Activity ◽  
Cytochrome P450 ◽  
Liver Injury ◽  
Hepatic Blood Flow ◽  
Guinea Pigs ◽  
Cytochrome P450 Enzyme ◽  
P450 Enzyme

scholarly journals Physiologically based modeling of the effect of physiological and anthropometric variability on indocyanine green based liver function tests

2021 ◽  
Author(s):  
Adrian Köller ◽  
Jan Grzegorzewski ◽  
Matthias König
Keyword(s):  
Blood Flow ◽  
Body Weight ◽  
Liver Function ◽  
Indocyanine Green ◽  
Hepatic Blood Flow ◽  
Liver Function Tests ◽  
Individual Variability ◽  
Hepatic Elimination ◽  
Function Tests ◽  
Physiologically Based

Accurate evaluation of liver function is a central task in hepatology. Dynamic liver function tests (DLFT) based on the time-dependent elimination of a test substance provide an important tool for such a functional assessment. These tests are used in the diagnosis and monitoring of liver disease as well as in the planning of hepatobiliary surgery. A key challenge in the evaluation of liver function with DLFTs is the large inter-individual variability. Indocyanine green (ICG) is a widely applied test compound used for the evaluation of liver function. After an intravenous administration, pharmacokinetic (PK) parameters are calculated from the plasma disappearance curve of ICG which provide an estimate of liver function. The hepatic elimination of ICG is affected by physiological factors such as hepatic blood flow or binding of ICG to plasma proteins, anthropometric factors such as body weight, age, and sex, or the protein amount of the organic anion-transporting polypeptide 1B3 (OATP1B3) mediating the hepatic uptake of ICG. Being able to account for and better understand these various sources of inter-individual variability would allow to improve the power of ICG based DLFTs and move towards an individualized evaluation of liver function. Within this work we systematically analyzed the effect of various factors on ICG elimination by the means of computational modeling. For the analysis, a recently developed and validated physiologically based pharmacokinetics (PBPK) model of ICG distribution and hepatic elimination was utilized. Key results are (i) a systematic analysis of the variability in ICG elimination due to hepatic blood flow, cardiac output, OATP1B3 abundance, liver volume, body weight and plasma bilirubin level; (ii) the evaluation of the inter-individual variability in ICG elimination via a large in silico cohort of n=100000 subjects based on the NHANES cohort with special focus on stratification by age, sex, and body weight; (iii) the evaluation of the effect of various degrees of cirrhosis on variability in ICG elimination. The presented results are an important step towards individualizing liver function tests by elucidating the effects of confounding physiological and anthropometric parameters in the evaluation of liver function via ICG.

Bedside micro-method for measuring effective hepatic blood flow, with use of first-order galactose clearance pharmacokinetics.

1985 ◽  
Vol 31 (9) ◽  
pp. 1557-1559 ◽  
Author(s):  
E B Rypins ◽  
H Sankary ◽  
M J Wynn
Keyword(s):  
Blood Flow ◽  
Steady State ◽  
Hepatic Blood Flow ◽  
Small Sample ◽  
Galactose Oxidase ◽  
Laboratory Animals ◽  
Constant Infusion ◽  
Metabolic Clearance ◽  
First Order ◽  
Hepatic Diseases

Abstract Data from first-order galactose clearance were used to estimate "effective" hepatic blood flow in normal subjects and in patients with hepatic diseases. Galactose clearance was determined by infusing galactose intravenously at a constant rate and measuring its resulting steady-state concentration in blood. The infusion rate must not exceed the maximum rate of galactose clearance by the liver, the "galactose elimination capacity." With this constraint and within the physiological and pathophysiological limits of hepatic blood flow, a constant infusion at 50 mg/min results in steady-state concentrations ranging from 20 to 200 mg/L. To measure galactose within this range, we modified a YSI Model 23A glucose analyzer and, using an immobilized galactose oxidase (EC 1.1.3.9)/hydrogen peroxide electrode system, accurately measured galactose in water and blood. The galactose metabolic clearance rate was calculated for six normal rats and for a normal and a cirrhotic human subject. The speed of the analysis (40 s), the small sample required (25 microL), and the suitability of fresh whole blood as the sample make the method ideal for measuring hepatic blood flow in small laboratory animals as well as for determining at bedside the effective hepatic blood flow in humans.

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