Intro to Pharm and Tox Topics   

Clearance and Extraction Ratio

As discussed previously, the 3 fundamental paramenters of pharmacokinetics are clearance, volume of distribution and bioavailability. Clearance is the most important paramenter; is an index of efficiency of drug elimination.

  Cl   =   Ke Vd

The main tissues responsible for elimination are the liver (metabolism) and kidneys (excretion). Therefore, the overall excretion rate and clearance have as component the liver and kidney paramenters:

excretion = renal excretion + hepatic metabolism

   Cl Cp     =        ClR Cp        +         ClH Cp

      Cl       =           ClR          +           ClH

Renal excretion can calso be calculated from the blood flow through the kidneys (QR):

renal excretion = Cdrug QR
                                  Cp  

(what is Cdrug ?? sorry... this is getting sketchy...)

excretion = Cl Cp    ==integrate==>   DoseIV = Cl • AUC

where AUC = area under the curve. This is only true when there is complete absorption (IV dose). If there is not complete absorption, then:

Fpo Dosepo = Cl • AUCpo

=> Cl = Fpo Dosepo = Doseiv
                 AUCpo         AUCiv

=> Fpo = AUCpo • Doseiv
               Dosepo    AUCiv

(if you understood any of this, please explain it to me! toxchick@lycos.com)

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