When we measure plasma clearance, we often compare to the hepatic bloodBack to the Top
flow (for instance 21 ml/min/kg in the man). If you measure blood
clearance, due to a high blood partitioning, do you still use the same
value of hepatic blood flow ?
If we start with the value of 21 ml/min/kg as hepatic blood flow in the
human, do we must compare the blood or the plasma clearance ?
Thank you very much for your help
Jean michel linget
ADME/tox
CareX
Dear Jean Michel,Back to the Top
You wrote:
"When we measure plasma clearance, we often compare to the hepatic blood
flow (for instance 21 ml/min/kg in the man). If you measure blood
clearance, due to a high blood partitioning, do you still use the same
value of hepatic blood flow ?"
IHMO, this question depends on the rate of drug transport between
plasma and blood cells:
1) If this transport is fast, i.e. if equilibrium is maintained during
passage of the liver, comparison of clearance to hepatic blood flow
makes sense only if the clearance is converted to blood clearance. Using the
notation proposed by Rowland, the elimination rate is proportional to
both plasma concentration and blood concentration:
elimination rate = CL . C = CLb . Cb
where the subscript b refers to blood and the symbols without subscript
to plasma.
Assuming a fixed and known ratio of Cb and C, CLb can be calculated
from CL and Cb/C.
2) If the transport is slow, i.e. if the concentration of drug in blood
cells is not changing during passage of the liver: in this case, hepatic
blood flow should be converted to hepatic plasma flow using the
hematocrit
value.
I would assume that #1 is the usual case, but I am definitely not sure
about this. Any comments?
Best regards,
Hans Proost
Johannes H. Proost
Dept. of Pharmacokinetics and Drug Delivery
University Centre for Pharmacy
Antonius Deusinglaan 1
9713 AV Groningen, The Netherlands
tel. 31-50 363 3292
fax 31-50 363 3247
Email: j.h.proost.-at-.farm.rug.nl
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