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How to better this fitting "lacidipine" #411

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wangwei1619 opened this issue Oct 30, 2019 · 0 comments

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@wangwei1619
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@wangwei1619 wangwei1619 commented Oct 30, 2019

Hi, all
I am trying to duplicate the simulation of lacidipine on beagles from two papers (DOI: 10.1039/c4ra16017g, and DOI: 10.1016/j.ajps.2016.03.003).
I used i.v. (0.5mg/kg) data and oral suspension (2mg/kg)data to fit my parameters:
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Then I simulate some oral formulations (single 4mg) by combination with dissolution profile, but result is not very satisfactory:
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For fitting process, the log P, solubility, hepatic clearance, permeability, intestinal permeability, gastric emptying time, small and large intestinal transit time were adjusted. For the subsequent simulations, only three time-related parameters were adjusted. The huge difference can been seen in formualtion A and T1. Is there any way to futher better this simulation?

The PK-Sim file and two papers has been attached to this issue.
Ladicipine.zip

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