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(1) The liver is the main organ of drug metabolism, but not the only way of drug elimination. There is also renal elimination, etc.
(2) The drug is unstable in the blood, and the clearance of the drug does not have a hepatic effect.
(3) In some cases, when the drug concentration in red blood cells is much higher than that in plasma, the calculation of proper clearance cannot be approximated by the drug concentration in plasma.
(4) In individual cases, metabolism or uptake by the lungs occupies a significant role.