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Hi,
I have some questions that I couldn't quite figure out:
I was using hepatic microsomes from two different mouse strains to
look at the in vitro metabolism of two different substrates (both of
which are metabolized by the same enzyme) and their Vmax values are:
Strain A Strain B
--
Substrate A 0.58 0.50
Substrate B 0.10 0.04
Correct me if I am wrong, if both substrates are metabolized by the
same enzyme in either strains, shouldn't the Vmax of Substrate B be
more similar between Strain A and B?
Second parts of the question:
I have obtained the following in vivo PK parameters of a drug in two
different mouse strains:
Strain A Strain B
--
AUC 92.9* 80.8
T1/2 8.6 9.2
CL/F 4.5* 5.2
Tmax 10.0 10.0
Cmax 201* 160
V/F 56.6 80.2
--
*<0.05
I understand that the higher Cmax and AUC is due to lower CL/F and
lower V/F, however, what I don't understand is how despite similar
T1/2, there is no difference in CL/F? I hope I am making some sense...
Thanks in Advance.
Eric
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I assume your in vivo data is after PO administration under identical
conditions (formulations, fed/fasted status).Do you have any std. dev.
values associated with PK parameters of AUC and Cmax? In strain B,
high V/F may contribute to longer t1/2.
In your microsome assay, have you considered correction for microsomal
binding?
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Hi Satya,
The in vivo data is from SC treatment (identical between strains).
Strain A Strain B
AUC 92.9+/-2.9* 80.8+/-3.2
Cmax 201+/-15* 160+/-15
For the microsomal assay, we didn't correct for microsomal binding.
Thanks,
Eric
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Just for clarity what are the data? X=B1SD or X=B1SEM? What is the number?
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