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When I read some textbook on PK, there are some views that really confusing me. Would you please
feel free give your comments to specify them?
1) "Plasma clearance if often found to be greater than the blood flow rate of the eliminating
organ(s) such as the liver, which is the upper limit of the organ clearance. This may indicate the
drug partitions more to red blood cells than to plasma, and drug molecules bound to red blood cells
are also available for extraction by the organ."
Any comments on these views will be highly appreciated.
Thanks in advance,
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First, assume that the liver is the only eliminating organ. The amount of drug eliminated per unit
of time can never be larger than the amount of drug entering the liver per unit of time. This amount
of drug eliminated per unit of time, or elimination rate, is usually denote as a differential
quotient dA/dt, where A is the amount in the body. Now we define plasma clearance (CL) and blood
dA/dt = CL * C = CLb * Cb
where C is the plasma concentration entering the liver (i.e. in the system) and Cb is the
corresponding blood concentration.
CLb cannot be larger than the liver blood flow Qh, as a result of the above restriction. This can be
CLb = Eh * Qh
where Eh is the hepatic extraction ratio (between 0 and 1)
For drugs partitioning more to red blood cells than to plasma, the blood concentration Cb exceeds
the plasma concentration C. To maintain the above equation (which is true by definition), CL can be
CL = CLb * Cb / C = Eh * Qh * Cb / C
CL will be higher than Qh if the product of the extraction ratio Eh and the blood/plasma ratio Cb/C
exceeds 1. This will occur only if Eh is high (close to 1), and the blood/plasma ratio Cb/C (well
Johannes H. Proost
Dept. of Pharmacokinetics, Toxicology and Targeting
University Centre for Pharmacy
Antonius Deusinglaan 1
9713 AV Groningen, The Netherlands
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