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Dear all,
I want to calculate intrinsic clearance in Human liver microsomes
There 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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In vitro intrinsic clearance can be calculated in terms of ml/min/mg using:
Cl = (ln 2 * ml incubation) / (T ½ * mg protein)
Regards
Mike
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Dear Sir,
We cannot fit any compartment model in the in vitro microsomal studies. You can use following
equations 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/gm
Liver) x (gm of liver/kg of body weight)
Regards,
Abhisheak
Abhisheak Sharma, Ph.D.
Post-doctoral Research Associate
Department of Pharmaceutics & Drug Delivery
The University of Mississippi
101 Faser Hall,
University, MS 38677, United States (US)
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Hi,
What is the time of incubation? For how long you are conducting the incubation? Biphasic = 2
different slopes of substrate depletion = 2 different processes of substrate depletion (please
correct me if I am inferring wrongly). Now, if that was hepatocytes, we could have said uptake was
involved, but would like to know what are the reasons that can cause this biphasic substrate
depletion in HLM?
MBI is possible perhaps
Regards
Sagnik
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Please refer to "Predicting clearance in humans from in vitro data" by R Scott Obach published in
Curr Top Med Chem. 2011;11(4):334-9. for a thorough guidance.
Regards,
Amir
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