Analysis of in vitro data from whole cell systems and dissolution studies is complex, challenging, and time consuming. Yet, accurate data analysis and informed data interpretation early in the drug development process are crucial for success. This is especially necessary as the drugs and formulations increase in complexity.
The Simcyp™ In Vitro Data Analysis Toolkit (SIVA) is a user-friendly, software solution to help you analyze complex in vitro studies, including those with whole cells, tissue samples and solid dosage forms, to assess the exposure, metabolism, transport, and dissolution/solubility of drugs. Other tools have mainly been developed for broader data analysis and not specifically designed for in vitro systems, do not readily support analysis via state-of-the-art models, and do not automatically incorporate statistical rigor.
The SIVA Toolkit platform is designed to analyze complex in vitro data, providing accurate values for parameters that can subsequently be used in in vitro-in vivo extrapolation paradigms that are necessary to successfully predict in vivo behavior of drugs in physiologically-based pharmacokinetic (PBPK) models.
- Simultaneous modeling of multiple experiments, resulting in improved confidence in estimates
- Incorporation of statistical rigor via goodness of fit measurements and diagnostic plots, with automated plots generated after fitting
- Automated IVIVE enabling integration of in vitro metabolic clearance data and physiological scaling factors for extrapolation of hepatic clearance for multiple species (human, dog, rat, mouse)
- Predicting ADME parameters using in silico models (e.g., fraction of unbound drug in plasma, blood-to-plasma ratio)
- Prediction of intracellular operating concentrations driving qualitative and quantitative in vitro endpoints
The SIVA toolkit contains a pre-defined library of models for analyzing in vitro data in the following areas:
- Metabolic Intrinsic Clearance
- Mechanistic Permeability and Transporter Substrate/Inhibitor
- Mechanistic Enzyme Inhibition
- Dissolution and Precipitation
- Drug Solubility
- Virtual In Vitro Distribution
- Surface pH (Dissolution Models)
Examples of in vitro assays and dissolution tests for which mathematical models are available within the SIVA Toolkit.
- Cellular Uptake
- Transwell Assays
- Cellular Uptake and Biliary Clearance
- USP II and µDiss Dissolution Apparatus
- Up to 3 Vessel Dynamic Transfer Model with time-variant media composition
- USP IV Dissolution Apparatus
- USP II Biphasic dissolution experiments
- Serial Dilution dissolution experiments