# PharmPK Discussion - Partial metabolic clearance

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• On 1 Feb 2001 at 17:08:21, =?iso-8859-1?Q?=22Masson=2C_=C9ric=22?= (emasson.at.anapharm.com) sent the message
`The following message was posted to: PharmPKAssuming a single dose or drug (A) is administered, and converted into anintermediate metabolite (B) which is converted to a final metabolite (C).My question is regarding the partial metabolic clearance:1- Which of the following equation is valid, if any, to calculate thepartial metabolic clearance of metabolite C:CLmet C = Ae0-inf. (C)/ AUC0-inf. (parent A)CLmet C=  Ae0-inf. (C)/ AUC0-inf. (met. B)Clmet C=  Ae0-inf. (C)/ AUC0-inf. (met. A+B)2- Is this parameter valid even when the metabolic pathways are not fullycharacterized?Any insight or references would be appreciated.Eric Masson`
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• On 2 Feb 2001 at 15:18:28, Khalid Alkharfy (khast6+.-a-.pitt.edu) sent the message
`The following message was posted to: PharmPKDear Eric:Your scenario is as follows:A------------>B------------>C   (assuming that this is the only metabolicpathway occurring)If you are interested in the calculating the formation clearance of C [CLfC], and the conversion of B------->C is the RATE LIMITING STEP, you shoulduse:CLf C=  Ae0-inf. (C)/ AUC0-inf. (met. B), assuming that C is totally renallyeliminated.To calculate the renal clearance of C [CL r C], use the following equation:CLr C=  Ae0-inf. (C)/ AUC0-inf. (met. C)However, if the rate limiting step is the conversion of A----------->B, youcannot directly calculate the CLf C from A, and you may need to administerthe intermediate metabolite B (if possible), then calculate the CLf C as:CLf C=  Ae0-inf. (C)/ AUC0-inf. (met. B)If the metabolic pathways are not well characterized, then the parametersthat you will be getting may not be accurate since the assumptions have beenviolated.You may want to administer the parent drug and measure the metabolites in theurine and do a mass balance study.Hope this helps.Thanks,Khalid AlkharfyUniversity of Pittsburgh.`
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