Hepatic clearance of drug

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. 

The hepatic clearance of drugs with an intermediate extraction ratio (Eh, 0.3-0.6) is affected by all three physiological variables blood flow to the liver, the unbound fraction in blood and the activity of hepatic drug-metabolizing enzymes. Disease-induced changes in the disposition of these drugs is least predictable. 

IMPAIRED HEPATIC CLEARANCE OF DRUGS The effect of liver disease on the hepatic biotransformation of drugs cannot be predicted from any measure of hepatic function. Thus, even though the metabolism of some drugs is decreased with impaired hepatic function, there is no quantitative basis for dose adjustment other than assessment of the clinical response and plasma concentration. The oral bioavailability of drugs with extensive first-pass hepatic clearance (e.g., morphine, meperidine, midazolam, and nifedipine) may be increased in liver disease. 

Pang KS, Rowland M. Hepatic clearance of drugs. II. Experimental evidence for acceptance of the well-stirred model over the parallel tube model using lidocaine in the perfused rat liver in situ preparation. J Pharmacokinet Biopharm 1977b 5 655-680. 

From Chapter 4 (Eq. 4.12) we know that hepatic clearance of drug may be defined as ... 

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