251
Views
68
CrossRef citations to date
0
Altmetric
Research Article

Progress Towards Prediction of Human Pharmacokinetic Parameters from In Vitro Technologies

&
Pages 393-415 | Published online: 12 Aug 2003
 

Abstract

This review provides an academic view of the current status on using in vitro systems for the prediction of human in vivo drug clearance and inhibition interaction potential. It stresses that although in vitro technology continues to develop in an impressive way and expectations are high within the pharmaceutical industry, the potential of prediction process is yet to be fully realized. The principles of scaling and modeling in vitro parameters have a sound base and have been validated by using animal tissue. However, it is clear that the comparatively simple standard approach developed and validated in animal systems, results in a high incidence of underprediction for parameters describing clearance and inhibition interaction potential when applied to humans. There are several challenges to our ability to interpret the human in vitro data that can now be so readily generated, in particular, accommodating the unusual kinetic properties characteristic of CYP3A4 substrates, namely, positive and negative cooperativity, in the assessment of inhibition potential.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.