Blood flow, hepatic

Kessler, B.J., Liebler, J.B., Bronfin, G.J. and Sass, M. (1954). The hepatic blood flow and splanchnic oxygen consumption in alcoholic fetty liver. J. Clin. Invest. 33, 1338-1345. 

Thus, if the hepatic clearance for a drug is largely relative to the hepatic blood flow, the extent of availability for this drug will be low when it is given by a route that yields first-pass effects. The decrease in availability is a function of only the anatomical site... 

Metabolism J. Hepatic blood flow J. Liver size J. Phase I metabolism 1 Incidence liver dysfunction T t /2 hepatically extracted drugs... 

KS Pang, M Rowland. Hepatic clearance of drugs. I. Theoretical considerations of a well-stirred model and a parallel tube model. Influence of hepatic blood flow, plasma and blood cell binding, and the hepatocellular enzymatic activity on hepatic drug clearance. J Pharmacokin Biopharm 5/6 625-653, 1977. 

Both ADH and ALDH use NAD+ as cofactor in the oxidation of ethanol to acetaldehyde. The rate of alcohol metabolism is determined not only by the amount of ADH and ALDH2 enzyme in tissue and by their functional characteristics, but also by the concentrations of the cofactors NAD+ and NADH and of ethanol and acetaldehyde in the cellular compartments (i.e., cytosol and mitochondria). Environmental influences on elimination rate can occur through changes in the redox ratio of NAD+/NADH and through changes in hepatic blood flow. The equilib-... 

Spontaneous bacterial peritonitis (SBP) is a serious complication of cirrhotic ascites, arising most frequently in those with advanced liver disease. Its development leads to a further reduction in the effective arterial blood volume, and it has a mortality rate equivalent to that of a variceal bleed [202], Since hepatic blood flow and func-... 

Liver i Hepatic size i Hepatic blood flow... 

Pirttiaho HI, Sotaniemi EA, Pelkonen RO et al (1982) Hepatic blood flow and drug metabolism in patients on enzyme-inducing anticonvulsants. Eur J Clin Pharmacol 22 441-445... 

T5. Tygstrup, N., and Winkler, K., Galactose blood clearance as a measure of hepatic blood flow. Clin. Sci. 17, 1-9 (1958). 

Metabolism Hepatic metabolism may be reduced Decreased hepatic blood flow. Decreased liver mass. Diminished enzymatic function Important for some drags Verapamil and teophylline... 

If reduced plasma clearance of BSP were related to anesthetic induced alterations in hepatic blood flow it should be evident early in the course of the intoxication when these types of effects would be most pronounced. We have reported that significant plasma retention of BSP in rainbow trout occurred only within the first 24 h after treatment with MCB... 

An implication of the high degree of hepatic extraction is that clearance of nicotine should be dependent on liver blood flow. Thus, physiological events, such as meals, posture, exercise, or drugs perturbing hepatic blood flow, are predicted to affect the rate of nicotine metabolism. Meals consumed during a steady state infusion of nicotine result in a consistent decline in nicotine concentrations, the maximal effect seen 30-60 min after the end of a meal (Gries et al. 1996 Lee et al. 1989). Hepatic blood flow increases about 30% and nicotine clearance increases about 40% after a meal. 

The estimation of systemic clearance together with this value gives valuable information about the behaviour of a drug. High clearance drugs with values approaching hepatic blood flow will indicate hepatic extraction (metabolism) as a reason for low bioavailability. In contrast poor absorption will probably be the problem in low clearance drugs which show low bioavailabilities. 

The equation can be solved for intrinsic clearance (Clj) based upon systemic clearance (Clj) obtained after i.v. administration and hepatic blood flow (Q) in the test species. Intrinsic clearance in man can then be estimated based upon relative in vitro microsomal stabibty and the equation solved to provide an estimate for human systemic clearance. Hence this approach combines aUometry (by considering differences in organ blood flow) and species-specific differences in metabolic clearance. 

Low hepatic extraction ratio and low protein binding to minimize reUance on hepatic blood flow. 

In addition to hepatic blood flow and function, ICG plasma clearance is also a useful prognostic factor for selecting patients for hepatectomy [1311. A majority of model systems developed for continuous hepatic function monitoring rely on the clearance profile of indocyanine green (ICG), which is the primary focus of this section. 

Pharmacokinetics When administered intravenously, ICG rapidly binds to plasma proteins and is exclusively cleared by the liver, and subsequently secreted into the bile [8]. This forms the basis of the use of ICG for monitoring hepatic blood flow and function. Two pharmacokinetics models, a monoexponential decay, which describes the initial rapid clearance of ICG with a half-life of about 3 minutes (Eq. (1)) and a bi-exponential model, which incorporates the secondary phase clearance with a longer half-life (Eq. (2)), describe total clearance of ICG from plasma [ 132]. For real-time measurements by continuous organ function monitoring, the mono-exponential decay is preferred. 

The use of ICG to measure hepatic blood flow and function by spectrophotmet-ric analysis of serial blood samples collected invasively was recognized more than 50 years ago [141], and the concept of non-invasive optical monitoring of physiologic function with ICG is not new [ 142 -146]. However, advances in optical technology and the availability of miniature lasers for biomedical applications have resulted in the development of faster, simpler, and reliable optical methods for monitoring physiologic functions in real-time. While most of these methods rely on the absorption properties of ICG for continuous hepatic func-... 

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