# PharmPK Discussion - Intrinsic clearance

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• On 11 Aug 2015 at 09:12:42, Nagsen Gautam (nagsengautam.aaa.GMAIL.COM) sent the message
`Dear all,I want to calculate intrinsic clearance in Human liver microsomesThere are four ways to calculate-1- Non-compartmental (Cl= Dose/AUC)2- One-compartment (Cl=Dose/AUC or V*0.693/t0.5)3- Two-compartment (Cl=Dose/AUC)4- Substrate depletion (Cl=V*0.693/t0.5)I am getting biphasic substrate depletion profile, which approach is the best??I argue either 1st or 3rd.I will appreciate your responses.Thanks,Nagsen Gautam`
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• On 11 Aug 2015 at 09:49:04, Michael Cameron (cameron.aaa.scripps.edu) sent the message
`In vitro intrinsic clearance can be calculated in terms of ml/min/mg using:Cl = (ln 2 * ml incubation) / (T ½ * mg protein)RegardsMike`
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• On 11 Aug 2015 at 09:49:50, Abhisheak sharma (pharma_abhi.at.hotmail.com) sent the message
`Dear Sir,We cannot fit any compartment model in the in vitro microsomal studies. You can use followingequations for calculation of intrinsic clearance (which are based upon V/k):1. t1/2= 0.693/k (k can be derived from elimination phase)2. CLint = k (min-1)x [Incubation Volume, ml]/[Microsomal Protein; mg]3. CLint,Hepatic=   k (min-1)x [Incubation Volume, ml]/[Microsomal Protein; mg] x  (mg protein/gmLiver) x (gm of liver/kg of body weight)Regards,AbhisheakAbhisheak Sharma, Ph.D.Post-doctoral Research AssociateDepartment of Pharmaceutics & Drug DeliveryThe University of Mississippi101 Faser Hall,University, MS 38677, United States (US)`
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• On 11 Aug 2015 at 17:47:27, Sagnik Chatterjee (sagnik.chatterjee.at.gmail.com) sent the message
`Hi,What is the time of incubation? For how long you are conducting the incubation? Biphasic = 2different slopes of substrate depletion = 2 different processes of substrate depletion (pleasecorrect me if I am inferring wrongly). Now, if that was hepatocytes, we could have said uptake wasinvolved, but would like to know what are the reasons that can cause this biphasic substratedepletion in HLM?MBI is possible perhapsRegardsSagnik`
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• On 11 Aug 2015 at 17:48:15, Amir Samaan Youssef (amirsamaan.-at-.gmail.com) sent the message
`Please refer to "Predicting clearance in humans from in vitro data" by R Scott Obach published inCurr Top Med Chem. 2011;11(4):334-9. for a thorough guidance.Regards,Amir`
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