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Hi,
We recently had a compound with reasonable t1/2 (>60 min) in human microsome and S9 fractions. But its t1/2 in mouse microsome and S9 fractions was short (<25 min). In vivo DMPK studies suggested this compound had good F% (65%) and high clearance. Upon IV injection, its concentration in plasma was quite low. To clarify the reasons, what kind of experiments we need to run quickly? Of course, last time we did not run protein binding and plasma stability studies as well as renal clearance.
Thanks for the help,
Patrick
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I'd suggest an 14C autoradiography to see accumulation tissue,
Dominique
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Try running blood to plasma ratios to see which compartment the drug is in and use the ratio to estimate blood concentration from plasma concentrations.
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Hello Patrick,
I would like to ask you in return one question. You have conducted invitro drug stability in microsome and S9 fraction, wherein you will come to know your drugs metabolism. What if your drug is getting eliminated as such through urine? You can check the concentration of drug in urine samples. Also evaluating the stability of your drug in plasma is worth considering.
Regards
Anasuya Patel
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