Development of State of the Art Application Software Capable of Assessing Clinically Relevant Drug-Drug Interactions by Fujitsu Kyushu Systems Limited
A drug-drug interaction or otherwise referred to as DDI is a pharmacological phenomenon whereby the presence of a second drug (inhibitor) alters the behavior and response of the body to a given dose of a first drug (substrate) leading to changes in the efficacy and safety of drugs when the two drugs are administered together, resulting in adverse side effects or even sometimes fatal death.
Generally, many drug candidates are identified by pharmaceutical companies based on highly specialized and target-specific assay systems which were then optimized and carefully screened through meaningful in vitro assays and animal studies; however still a number of these drug candidates fail in clinical trials (or even drop out of the market after they have been released) mostly due to safety reasons, one of them being potentially deadly DDI.
The need to early detect such unwanted DDIs would help save pharmaceutical companies from the costly and frustrating attrition of drugs at the later phase of drug development. Based on this need, Fujitsu Kyushu Systems Limited (FJQS) has developed DDI Simulator, a state of the art software designed specifically to help the pharmaceutical companies assess the risk of clinically relevant DDIs.
The DDI Simulator was developed based on the results of the DDI database project sponsored by the Human Animal Bridging Research Organization (HAB), a nonprofit research organization in Japan. The application software features an intuitive interface and a new model to evaluate mechanism-based inhibitions (MBI) which was introduced in to the DDI Simulator under the supervision of Professor Yuichi Sugiyama of Tokyo University, helping researchers to perform DDI simulations more effectively.
The capability of DDI Simulator extends to allow users perform quantitative simulation of the clinical behavior of a substrate drug, with or without the influence of an inhibitor, which is based on input pharmacokinetic parameters and through the use of physiologically-based mathematical models. The physiologically-based pharmacokinetic (PBPK) models used in simulations are openly available for verification by the users. In addition to these features, DDI Simulator includes a database of pharmacokinetic parameters (including in vivo Ki) of well-known substrates and inhibitors which are ready for use in simulations with the user’s own compound. (Fig1)
DDI Simulator would allow users to perform simulation addressing the issues including effect of simultaneous inhibition of multiple CYP isoforms and other drug metabolizing enzyme (Fig.2), as well as effect of inhibition of the intestinal metabolism (Fig.3).
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