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Can anyone provide a reference or two on the microsomal yield of mouse
liver (any strain)? Specifically, I'm looking for the mg microsomal
protein per g liver for use as a scaling factor for intrinsic
clearance. These values are easily available for rat, dog, human and
even many more exotic species, but surprisingly, I've found very
little published for the mouse.
Any help is greatly appreciated.
Peter Rix
Kalypsys, Inc.
San Diego, CA
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Hello Peter:
Surprisingly different values for MPPGL (mg protein per gram
liver) have been used as scaling factor. The generic value of 45 mg/g
MPPGL is derived from rat data (n=3?) that has been used extensively
to predict hepatic intrinsic clearance (Obach et al., 1999, Drug
Metab. Dispo. 27, 1350-1359).
Although MPPGL values used for the conversion of intrinsic clearance
per mg microsomal protein into that per g liver are reported in rats,
dogs and humans (Iwatsubo et al, JPET 283:462-469, 1997), no value is
available in literature for mouse, to my knowledge. We use 45 mg/g
MPPGL for mouse/rat and 32 mg/g MPPGL for human, derived from Barter
et al., (2007 Current Drug Metabolism 8:33-45).
As we are aware, CL int can be referenced to the amount of protein,
the number of cells, or CYP content (for drugs metabolized exclusively
by CYP's), then scaled to a value per gram of liver and Iwatsubo et
al, suggests the following scaling factors.
- 52.5 mg microsomal protein/g liver
- 0.14 nmol P450/106 cells
- 120 X106 cells/g liver
- 0.32 nmol P450/mg microsomal protein
Albeit incorporating mouse MPPGL value would improve accuracy, we must
understand that these reported values may differ between the
laboratories and hence should be used cautiously to provide reasonable
estimate when scaled to in-vivo.
I would highly appreciate further comments from experts of this forum
on this topic.
Thanks.
Regds,
SYED MUSTAFA,
Advinus Therapeutics Pvt. Ltd.,
International Biotech Park,
Genesis Square, Bio Resource Centre,
2nd Floor, Phase II, Hinjewadi,
Pune- 411 057
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The following message was posted to: PharmPK
Dear Peter,
Maybe in the interspecies database.
www.rivm.nl/interspeciesinfo/
Jos
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