How important is permeability on flux rate of drug from plasma to interstitial space (Jvi,org) for biologics PBPK? #431

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opened this issue Dec 5, 2019 · 5 comments
Open

How important is permeability on flux rate of drug from plasma to interstitial space (Jvi,org) for biologics PBPK?#431

opened this issue Dec 5, 2019 · 5 comments

SL-CHOI commented Dec 5, 2019 • edited

 Hello all, It is a question about equation 2 in paper "Christoph et al. 2018 A generic whole body physiologically based pharmacokinetic model for therapeutic proteins in PK-Sim". Equation 2 in the paper explicitly indicates product of permeability and surface area (PS,org) is a crucial factor to the flux rate of drug from plasma to insterstitial space (Jvi,org). On the other hands, Peclet numbers in equation 2, that defines ratio of convective and diffusive transport (Pe,org= J,org * (1-Sigma,org)/ PS,org), would cancel out PS,org in equation 2. As a result, Jvi,org is independent of PS,org. This makes me wonder the reason of having permeability (PS,org) in equation 2 from the paper.

StephanSchaller commented Dec 5, 2019

 But you still have the Peclet number in the exponent within the denominator in equation 2.

SL-CHOI commented Dec 5, 2019

 Yes, but Peclet number (Pe) is a ratio of extravasation-diffusive transport, which has a different physiological meaning as compared to PS,org for diffusive transport. When PS,org is cancelled out, how to explain the denominator term EXP(Pe)-1?

StephanSchaller commented Dec 5, 2019

 , how to explain the denominator term EXP(Pe)-1? Not sure I understand what you mean by this. Have you read up on the references from which these equations were derived: Ref. [46] should be helpful, e.g. Equation (5), some more on Peclet around Equation 17 and 33. @Christoph27 can you comment?

SL-CHOI commented Dec 7, 2019

 @StephanSchaller Thank you Stephan for pointing out that. We may find something out from Ref. 46.

StephanSchaller commented Dec 9, 2019

 @SL-CHOI, happy to help. Please do let us know if you find sth. out.