The Simcyp population-based ADME simulator[1] is a modelling and simulation platform used by the pharmaceutical industry in drug discovery and development. The Simulator models drug absorption, distribution, metabolism and elimination (ADME) using routinely generated in vitro data.
Simcyp simulations are performed in virtual populations, including paediatric populations, rather than an average individual. This allows individuals at extreme risk from adverse reaction to be identified prior to human studies.[2] The functional capability of the Simcyp Simulator are summarized in the following table.
| Metabolism | Identification of the extremes and determinants of population variability in in vivo drug metabolism from in vitro data generated using:
Human liver microsomes |
| PK profiles | Simulation of full drug and metabolite concentration–time profi les. Prediction of volume of distribution based on lipophilicity, ionisation, protein binding and tissue composition by reference to a 14 organ PBPK model |
| Drug – drug interactions | Prediction of the extent of metabolically-based drug–drug interactions, allowing simultaneous consideration of:
Competitive enzyme inhibition Irreversible, mechanism (time)-based enzyme inhibition (including auto-inhibition) |
| Absorption | The Simcyp advanced dissolution absorption and metabolism (ADAM) model incorporates factors influencing the rate and extent of oral drug absorption including: Gastric emptying rate and intestinal and colon transit times Regio- and age-specific luminal pH as it affects ionisation, solubility, chemical stability, permeability, dissolution and precipitation GI tract surface area and regional variation in permeability and enzyme and transporter density Luminal fluid volumes and dynamics Fed versus fasting states It allows evaluation of immediate and modified release formulations and the impact of particle size on dissolution rate |
| Virtual patient populations | Simcyp population databases include North European Caucasians, Japanese, healthy volunteers (for virtual Phase I studies) as well as obese/morbidly obese individuals and patients with renal impairment (moderate or severe), and liver cirrhosis (Child-Pugh A, B or C) |
| Trial design | Flexible trial design options facilitate different routes of drug administration and a variety of dosing options including single/multiple dosing and dose staggering |
| Paediatric | A full PBPK model, supported by extensive libraries on demographics, developmental physiology and the ontogeny of drug elimination pathways allows prediction of PK behaviour in neonates, infants and children |