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I have a question about designing a PK study for a compound. The
compound can lower blood pressure in pentobarbiturate- anesthetized
SD rats at a dose as low as 2 mcg/kg (IV bolus injection) and the
corresponding plasma concentration was approximately 1 ng/ml. When a
higher dose (>75 mcg/kg, IV) was applied, the compound triggers
convulsive reaction in the animals. We detected a plasma
concentration of 2500 ng/ml, following a 50 mcg/kg bolus injection.
When we orally dosed rats with the compound up to 20 mg/kg, we did
not observe any toxic responses and detected a concentration range
from 30 mcg/ml (15 min after the dosing) to 1.5 mcg/ml (24 hr
after). The estimated bioavailability is less than 5%. How should I
design the PK study for this compound? Is it a good lead? Thanks.
D. Wang
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Dear Wang,
I am interested in knowing why you did not observe any toxicity at a
concentration of 30mcg/mL (after PO administration) which is probably
far too higher than the concentration you would detect after 75 mcg/Kg
dose, thanks, Jagannath
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