Evaluation of various static and dynamic modeling methods to predict clinical CYP3a induction using in vitro CYP3A4 mRNA induction data
Clinical Pharmacology and Therapeutics, ISSN: 0009-9236, Vol: 95, Issue: 2, Page: 179-188
2014
- 79Citations
- 63Captures
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Example: if you select the 1-year option for an article published in 2019 and a metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019. If you select the 3-year option for the same article published in 2019 and the metric category shows 90%, that means that the article or review is performing better than 90% of the other articles/reviews published in that journal in 2019, 2018 and 2017.
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Metrics Details
- Citations79
- Citation Indexes77
- 77
- CrossRef69
- Policy Citations2
- Policy Citation2
- Captures63
- Readers63
- 63
Article Description
Several drug-drug interaction (DDI) prediction models were evaluated for their ability to identify drugs with cytochrome P450 (CYP)3A induction liability based on in vitro mRNA data. The drug interaction magnitudes of CYP3A substrates from 28 clinical trials were predicted using (i) correlation approaches (ratio of the in vivo peak plasma concentration (C max) to in vitro half-maximal effective concentration (EC 50); and relative induction score), (ii) a basic static model (calculated R 3 value), (iii) a mechanistic static model (net effect), and (iv) mechanistic dynamic (physiologically based pharmacokinetic) modeling. All models performed with high fidelity and predicted few false negatives or false positives. The correlation approaches and basic static model resulted in no false negatives when total C max was incorporated; these models may be sufficient to conservatively identify clinical CYP3A induction liability. Mechanistic models that include CYP inactivation in addition to induction resulted in DDI predictions with less accuracy, likely due to an overprediction of the inactivation effect.
Bibliographic Details
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84893723325&origin=inward; http://dx.doi.org/10.1038/clpt.2013.170; http://www.ncbi.nlm.nih.gov/pubmed/23995268; https://onlinelibrary.wiley.com/doi/10.1038/clpt.2013.170; https://dx.doi.org/10.1038/clpt.2013.170; https://ascpt.onlinelibrary.wiley.com/doi/10.1038/clpt.2013.170
Wiley
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