Hepatic clearance actual

If the rate of elimination decreases in Scheme 7.2, then what happens to clearance Clearance is unchanged. For each 4.0-second pass, the liver clears 50 mL (CLh = 12.5 mL/s) out of the total 100 mL of blood that flows through the organ. Literally, 50% of the blood volume is cleared, so the actual impact is a decrease in Cp by 50%. While clearance is constant, the effect of clearance on Cp varies with Cp. Clearance depends on the action of metabolic enzymes on the drug and, at very high drug concentrations, the enzymes can become saturated with substrate. Under these conditions, which are rare, clearance is not constant. Therapeutic concentrations of modem drugs are normally well below the concentrations required to saturate liver enzymes. The tubular secretion and reabsorption processes in the kidneys can also be saturated and affect renal clearance. As with hepatic clearance, variable renal clearance is rare. 

Table 8.2 Comparison of the predicted in vivo hepatic clearance and the actual clearance values for compound X...

Oral clearance is a common term used in the pharmaceutical industry to describe the apparent CL of an orally dosed compound, expressed as CL// = Dose/AUC. Oral clearance is the reciprocal of dose-normalized AUC. Oral clearance reflects the overall exposure efficiency, without differentiating the efficiency of compound delivery or elimination, while IV clearance only reflects the exposure efficiency caused by elimination. Oral clearance is equal or higher than IV clearance. When bioavailability is high, oral clearance is very close to IV clearance. If the bioavailability is low, either due to low absorption or high first-pass effect, oral clearance can be much higher than IV clearance. High oral clearance indicates very low exposure efficiency. When absorption is complete (Fa% = 100), oral CL is actually the intrinsic hepatic clearance for a compound when hepatic metabolism is the major elimination route. Neither oral clearance nor intrinsic CL is limited by the blood flow. 

Several tests have been developed to quantify actual liver function, including indocyanine green (ICG), aminopyrine and bromosulpho-thalein. The principle of these tests is to determine whether hepatic blood flow or cell function is reduced by administering a chemical which is exclusively taken up or metabolised by the liver. For example, in the ICG clearance test the ICG is a non-toxic chemical solely taken... 

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