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Dear all,
Does anyone have experience of IVIVC when working with a prodrug? I ask because I have plasma
concentration data of an active metabolite as well as in-vitro dissolution data of the prodrug, but
don’t really know how to put them together. Which input is needed (e.g. about the metabolism)?
Many thanks,
Johan
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Johan,
Concerning IVIVC when working with a prodrug, it should not be any different than working with the
drug. You just use the kernel that is the solution of the system following administration of the IV
(or of the immediate release or solution) of the drug to the concentrations of the metabolite. Not
much different from the regular case except that the function (solution of IV) could be more
complex. In most software packages this function is approximated by the sum of exponents. Or you can
use modeling software to recover it, and introduce the IVIVC into the model (following the ideas of
J Pharmacokinet Pharmacodyn. 2011 Jun;38(3):317-32. doi: 10.1007/s10928-011-9195-3. Epub 2011 Mar
16.
A population approach to in vitro-in vivo correlation modelling for compounds with nonlinear
kinetics.
Gaynor C1, Dunne A, Costello C, Davis J.
J Pharmacokinet Pharmacodyn. 2011 Oct;38(5):519-39. doi: 10.1007/s10928-011-9206-4. Epub 2011 Jul 7.
A time scaling approach to develop an in vitro-in vivo correlation (IVIVC) model using a
convolution-based technique.
Costello C1, Rossenu S, Vermeulen A, Cleton A, Dunne A.
Regards,
Leonid
Leonid Gibiansky,
QuantPharm LLC
www.quantpharm.com
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