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I need get liver extraction ratio through experiment. Both portal vein and Jugular vein are cannulated. Can I inject test article by Portal vein and Tail Vein, and sampling blood through jugular vein to get hepatic E?
Thanks
DM
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The following message was posted to: PharmPK
Dear Dean,
For the calculation of Liver extraction ratio we have cannulate portal vein by PE 50 tubing and blood circulated towards heart was blocked by artery forcep the drug containing buffer was passed from portal vein,considered as Q in and buffer cotaining drug collected through vena-cava by cannulation is considered as Q out it will reflect actual contribution of liver for metabolism of the drug which is infused though portal and collected by venacava by peristaltic pump.
So,calculated as Qin-Qout/Qin
Regards,
Sadanand Mallurwar,
DMPK,NDDD
Lupin Research park,Pune
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Dear Sadanand,
There is some correction in equation.
It will be ERatio=Q(Cin-Cout)/Cin.
Regards,
Rahul VAts
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Alternatively you can dose the test compound PO and collect HPV and systemic blood at different time points. AUCsys/AUC hpv will give you an idea about hepatic extraction
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The following message was posted to: PharmPK
Still not correct actually. Once the eliminating organ has reached distribution equilibrium:
Extraction Ratio = (Cin-Cout)/Cin
Best Regards,
Ian
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Dear Satya,
I would like to know procedure of collection of HPV at different time point because i once tried but rat died due to blockage of blood flow towards liver.
Regards,
Rahul Vats
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Try HPV Cannulation through sub branch and tie the knot towards GI not towards liver.
If you'll go for main branch sure rat will die.
try from any duodenal portal vein, it will merge in to HPV, so you'll get readings of HPV itself.
Regards,
Mitul Patel,
ADME Discovery Sciences,
Torrent Research Center.
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We infused midazolam at 0.5mg/kg for 10 min through portal vein and femoral vein, and blood samples were collected through jugular vein. But we have almost same AUC values between portal vein and femoral vein infusion.
Our experiment design is correct for getting liver E ?
Many thanks
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Dear Jean,
Midazolam is known for rapid metabolism via CYP enzymes.
If you want to calculate extraction ratio you can plan classical rat extraction model.
Infuse your drug solution dissolved in buffer through hepatic portal vein and collect the out put through inferior vena cava above the liver at different time points e.g. predose,1min,2min,3min,4min.
Find out the extraction ratio=Cin-Cout/Cin.
Make sure that your liver cells must be alive during the experiment.
Hope this will help.
Regards,
Rahul Vats
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