# PharmPK Discussion - Clearance greater than blood flow

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• On 23 Jul 2013 at 08:16:39, MJ sent the message
`Dear all,When I read some textbook on PK, there are some views that really confusing me.  Would you pleasefeel free give your comments to specify them?1)       "Plasma clearance if often found to be greater than the blood flow rate of the eliminatingorgan(s) such as the liver, which is the upper limit of the organ clearance.  This may indicate thedrug partitions more to red blood cells than to plasma, and drug molecules bound to red blood cellsare also available for extraction by the organ."Any comments on these views will be highly appreciated.Thanks in advance,MJ`
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• On 23 Jul 2013 at 08:59:36, Hans Proost sent the message
`Dear MJ,First, assume that the liver is the only eliminating organ. The amount of drug eliminated per unitof time can never be larger than the amount of drug entering the liver per unit of time. This amountof drug eliminated per unit of time, or elimination rate, is usually denote as a differentialquotient dA/dt, where A is the amount in the body. Now we define plasma clearance (CL) and bloodclearance (CLb)dA/dt = CL * C = CLb * Cbwhere C is the plasma concentration entering the liver (i.e. in the system) and Cb is thecorresponding blood concentration.CLb cannot be larger than the liver blood flow Qh, as a result of the above restriction. This can bewritten asCLb = Eh * Qhwhere 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 exceedsthe plasma concentration C. To maintain the above equation (which is true by definition), CL can bewritten:CL =  CLb * Cb / C = Eh * Qh * Cb / CCL will be higher than Qh if the product of the extraction ratio Eh and the blood/plasma ratio Cb/Cexceeds 1. This will occur only if Eh is high (close to 1), and the blood/plasma ratio Cb/C (wellabove 1).best regards,Hans ProostJohannes H. ProostDept. of Pharmacokinetics, Toxicology and TargetingUniversity Centre for PharmacyAntonius Deusinglaan 19713 AV Groningen, The Netherlands`
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