What is it about?
A new simple and accurate dynamic and static simulation method for DDI.
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Why is it important?
Consideration of hepatic extraction kinetics for both a victim and a perpetrator on the basis of the combination of tube and well-stirred models. It was found that the hepatic extraction ratio of a rapidly eliminating victim drug (typical example, ramelteon) has a great impact on DDI. This impact cannot be explained by any traditional well-stirred based methods. Moreover, the method is very practical, employing a two-compartment model based mathematical equations which can be calculated with a common tool for PC (Excel).
Perspectives
I was in charge of pharmacokinetics and bio-analysis of various types of preclinical and clinical compounds in Takeda Pharmaceutical Ind during 2000 to 2005. In those years, I encountered an unusual DDI between ramelteon (melatonin agonist) and fluvoxamine where the AUC of ramelteon was increased almost 130 fold. This cannot be predicted by any traditional methods. Since then, my research interest has been how to predict this type of drug-drug interaction. The method is actually useful to estimate in vivo Ki in DDI caused by any perpetrators and victims.
Dr Katsumi Iga
Doshisha Joshi Daigaku
Read the Original
This page is a summary of: Simulation of Metabolic Drug-Drug Interactions Perpetrated by Fluvoxamine Using Hybridized Two-Compartment Hepatic Drug-Pool-Based Tube Modeling and Estimation of In Vivo Inhibition Constants, Journal of Pharmaceutical Sciences, October 2015, Elsevier,
DOI: 10.1002/jps.24549.
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