# PharmPK Discussion - Biliary clearance calculations from liver perfusion studies

PharmPK Discussion List Archive Index page
• On 25 May 2005 at 03:40:40, "Andrew Powell" (andrew.powell.-at-.vcp.monash.edu.au) sent the message
`The following message was posted to: PharmPKHi all,In the recirculation-mode perfused liver preparation, it is myunderstanding  that biliary clearance is calculated (in the same way asrenal clearance in  vivo) as:CL(bile) = Mass(bile)/AUC(0-inf)Where Mass(bile) = the total mass of material recovered in bile (overinfinite time) and where AUC(0-inf) = the AUC under the perfusateconcentration vs. time profile.I have a feeling that the same equation cannot be applied in thesingle-pass  liver perfusion (conducted in a loading-washout design) .....Am I correct  in this?If I am correct, can anyone advise what is the appropriate equation fordetermining biliary clearance (CLbile), particularly in the case whensteady-state (with regards to outflow perfusate/bile concentrations) isnot  achieved before the washout phase is commenced?Finally, can anyone point me in the direction of a good description of the mathematical treatment of various perfusion designs?Thanks in advance!`
Back to the Top

• On 27 May 2005 at 13:19:10, "J.H.Proost" (J.H.Proost.aaa.rug.nl) sent the message
`The following message was posted to: PharmPKDear Andrew,You wrote: > biliary clearance is calculated as: CL(bile) = Mass(bile)/AUC(0-inf) > I have a feeling that the same equation cannot be applied in thesingle-pass  liver perfusion Am I correct  in this?Defining biliary clearance as the rate of biliary excretion divided by theperfusate concentration, this equation can be used. The way of drugadministration, in this case recirculatory or single pass, does not make adifference.Please note that for high-extraction drugs the 'perfusate concentration'may refer to the concentration entering the liver or leaving the liver, orsome average concentration; this makes a large difference! Usually,assuming the well-stirred model, the outlet concentration is used.Best regards,Hans ProostDept. of Pharmacokinetics and Drug DeliveryUniversity of Groningen, The Netherlands`
Back to the Top

• On 28 May 2005 at 12:00:32, "Candice B. Kissinger" (candice.at.bioanalytical.com) sent the message
`The following message was posted to: PharmPKReferring back to the original posting by Andrew Powell, and the recentone by Hans Proost on this subject...is everyone talking about an in vitromodel with an excised liver, or is this an anesthetized animal model?  Iam curious about whether these equations would also apply to an in vivomodel in a conscious, freely-moving animal?  Would collection and analysisof portal blood (to provide the AUC of the test article) and simultaneouscollection of bile (to provide the Mass(bile)portion) be applicable tothis  equation? Should we be providing a continuous infusion of testarticle (e.g. continuous gastric or duodenal infusion) to establishsomething analogous to a steady-state in the portal blood?  Under suchconditions, I wouldn't be surprised if CL increased dramatically vs. ananesthetized model, or an in vitro model.  Like Andrew, I'm seeking thebest way to represent it.Thanks for your opinions!Candice KissingerBASi`
Back to the Top

• On 31 May 2005 at 09:42:56, "Hans Proost" (j.h.proost.-at-.rug.nl) sent the message
`The following message was posted to: PharmPKDear Candice,The equation applies equally well to the in vivo situation, and is notrestricted to steady-state conditions. The choice of the sampling site iscritical, as I explained in my earlier message. In the case of in vivoanimal studies, the logical choice is to use 'normal' plasma concentrationsfor the calculation of AUC. The calculated biliary clearance (Total amountexcreted into bile divided by AUC) is then interpreted as the amount ofplasma cleared from the drug via the bile per unit of time (and thus acertain fraction of the total clearance). It does not necessarily reflectthe capacity of the liver to clear drugs via the biliary route; in case of ahigh hepatic extraction, the 'effective' concentration 'driving' the biliaryexcretion is lower than the central plasma concentration. So the appropriatesite of measurement depends on what you want to know.Hans ProostJohannes H. ProostDept. of Pharmacokinetics and Drug DeliveryUniversity Centre for PharmacyAntonius Deusinglaan 19713 AV Groningen, The Netherlandstel. 31-50 363 3292fax  31-50 363 3247Email: j.h.proost.aaa.rug.nl`
Back to the Top

Want to post a follow-up message on this topic? If this link does not work with your browser send a follow-up message to PharmPK@boomer.org with "Biliary clearance calculations from liver perfusion studies" as the subject

Copyright 1995-2010 David W. A. Bourne (david@boomer.org)