Flow-limited clearance

EIGURE 6.1 Plot of dialysis clearance (CL]j) vs. dialyzer blood flow (Q). The theoretical curves were fit to experimental data points to obtain estimates of the permeability coefficient-surface area product (P-S) for each solute. Flow-limited clearance is indicated by the dashed line. The data were generated with a Kolff-Brigham type hemodialysis apparatus. (Reproduced with permission from Renkin EM. Tr Am Soc Artific Organs 1956 2 102-5.)... 

Some drugs are metabolized so readily that even marked reduction in liver function does not significantly prolong their action. However, cardiac disease, by limiting blood flow to the liver, may impair disposition of those drugs whose metabolism is flow-limited (Table 4-7). These drugs are so readily metabolized by the liver that hepatic clearance is essentially equal to liver blood flow. Pulmonary disease may also affect drug metabolism, as indicated by the impaired... 

Table 4-7 Rapidly Metabolized Drugs Whose Hepatic Clearance Is Blood Flow-Limited. ...

Renkin used Equation 6.1 to estimate permeability coefficients for several solutes from flow and clearance measurements made on the Kolff-Brigham artificial kidney (Figure 6.1). This theoretical analysis seems reasonably consistent with the experimental results. In the Figure/ the dashed line indicates a flow limitation to transport because clearance can never exceed dialyzer blood floW/ a result that is obvious from inspection of Equation 6.1 (i.e./ is never less than 0). 

In this case, hepatic clearance is flozo limited, similar to the renal tubular excretion of p-aminohippurate. Because protein binding does not affect their clearance, drugs whose hepatic clearance is flow limited are said to be nonrestrictivehj eliminated and have extraction ratios > 0.7. 

Indocyanine green was introduced by J. Caesar et al. in 1961 as a liver function test. Anionic tricarbocyanine dye is referred to as an ideal test substance (1.) it is tolerated very well there have been no reports of any incidents so far, and even paravenous injection is tolerated (2.) it is excreted unchanged by hepatocytes in the bile as there is no bio transformation - this is why ICG clearance is valid as a measure of hepatocellular uptake and transport processes (3.) there is no interference with drugs (except rifamycin), haemolysis, bilirubin (up to approx. 4 mg/dl) or hyperlipidaemia (4.) the substance is not subject to the enterohepatic circulation (J.) the rapid elimination, which depends on hepatic perfusion ( flow-limited ), allows the calculation of the hepatic flow volume as a whole based on ICG clearance (6.) the method is simple to perform. 

Apparently verapamil is metabolized so rapidly that only the rate of delivery to the liver regulates its disappearance, ie, it is blood flow-limited. Further increases in liver enzymes could not increase its elimination. However, the rate of elimination of phenytoin is apparently limited by its rate of metabolism since clearance is much less than hepatic blood flow. Therefoiie, the clearance of phenytoin can rise if some agent causes an increase in liver enzymes. The answer is (C). 

Drugs that reduce hepatic blood flow, eg, propranolol, may also reduce the clearance of other drugs metabolized in the liver, especially those subject to flow-limited hepatic clearance such as morphine and verapamil. 

Due to necessary clearances needed for nonelectrified internal components at the top of wire-plate ESPs, part of the gas is able to flow around the charging zones. This is called "sneakage" and places an upper limit on the collection efficiency. 

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