How to report and discuss ADME data in medicinal chemistry publications: in vitro data or in vivo extrapolations?
2015 (English)In: Future Medicinal Chemistry, ISSN 1756-8919, E-ISSN 1756-8927, Vol. 7, no 3, 259-267 p.Article in journal (Refereed) Published
Early drug discovery projects often utilize data from ADME (absorption, distribution, metabolism, elimination) assays to benchmark and guide discussion, rather than the predicted in vivo consequences of these data. Here, the two paradigms are compared, using evaluations of metabolic stability based on either microsomal clearance assay data or from the predicted in vivo hepatic clearance and half-life calculated through the combination of the venous well-stirred model and Oie-Tozer's model. The need for a shift in paradigm is presented, and its implications discussed. It is suggested that discussions about ADME data should revolve around potential clinical problems that are most likely to surface during the development phase, each benchmarked with a suitable variable derived from the assay data.
Place, publisher, year, edition, pages
2015. Vol. 7, no 3, 259-267 p.
IdentifiersURN: urn:nbn:se:uu:diva-267082DOI: 10.4155/FMC.14.165ISI: 000362888800003PubMedID: 25826359OAI: oai:DiVA.org:uu-267082DiVA: diva2:872918