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I have a formulation and would like to know its brain penetration across the BBB in comparison to
conventional free drug. Hence i have conducted in vivo studies. Next, I have calculated my Kp value,
where Kp= AUCbrain/AUCplasma for both drug-encapsulated formulation and conventional free drug.
My problem is:
The formulation had a lower Kp value compared to free drug. BUT the concentration of formulation in
both blood and brain were much higher compared to free drug in blood and brain, suggesting that the
availability of the formulation were higher than the free drug (Good news!).
The formulation also had a significant reduction of elimination rate and clearance in the blood in
comparison to free drug.
I was thinking the low Kp value in the formulation was due to a much higher concentration of
formulation in the plasma (in companion of significant reduction in elimination rate, clearance and
Vd of formulation in plasma) compared to the brain.
Hence, my questions are:
1) Does a low Kp value suggest a poor brain penetrability?
2) Is Kp value suitable for my studies to predict the brain penetrability of formulation and drug?
3) Should i be using other parameter such as Kp,u or Kp, uu?
4) Does a lower Vd means the formulation did not bind to protein plasma, organ or the RES? As a
result, the clearance rate of the formulation was also subsequently reduced?
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