- On 7 Aug 2015 at 17:39:57, Qingrong Wang (freepig74.aaa.gmail.com) sent the message
Dear all,
We recently did IV infusion PK study in animal. The animal is 15kg, and plasma volume is about
450mL. The drug administration is 15mg for 1 hour constant IV infusion.
The plasma concentrations are: 0 h ((56 ug/mL), 1h (65 ug/mL), 2h(30 ug/mL), 3h(22 ug/mL), 4h(19 ug/mL), 6h(11 ug/mL), 8h(5.9 ug/mL),
10h (2.8ug/mL) 12h (1.5 ug/mL), 18h(0.4 ug/mL) 24h(0.2 ug/mL)
The Vss is about 150mL/kg. However, the plasma concentration at 1hr is 65mg/L. If its true that
means there are total 32.5mg drug in plasma in this time point. It is more than the administration
amount of drug.
Is something wrong of this time point? and why?
Best regards,
Alex
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- On 8 Aug 2015 at 08:35:31, Mutasim AL-Ghazawi (alghazam.-at-.ju.edu.jo) sent the message
Dear Alex
When you have the whole profile, then the volume of distribution is estimated from the administered
amount and concentrations. Thus one should not have that conflict. When a drug follows a multi
compartment model, Vss is not the appropriate volume at early times (before equilibrium is reached).
In such case Vc is the one to use. A small comment is that such volumes predict amount in the whole
body but not plasma only.
Prof. Mutasim Al-Ghazawi
The University of Jordan
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- On 8 Aug 2015 at 12:44:18, Chris Kemper (chris_kemper.-a-.pharmanavigatorsllc.com) sent the message
Alex:
Volume terms are tricky to interpret but let's consider boundaries. For the sake of argument, let's
assume that there is no distribution or clearance from the sampling compartment - plasma. With a
dose of 15 mg poured into a volume of 450 mL, the expected concentration is 33.3 mcg/mL. With
distribution and clearance processes, you would expect this number to be lower. This has to be the
upper boundary limit. Yet, you saw 65 mcg/mL. I do not see how that is physically possible. I would
check all these numbers and the materials and methods used in the study. I don't see this as a PK
analysis issue.
My two cents. But I am getting old.
Christopher J. Kemper, Ph.D.
Pharma Navigators, LLC
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