The statistical method, algorithm and methodology 5 Model qualification or val

The statistical approach, algorithm and methodology 5. Model qualification or validation criteria It should really be noted that the workflow and equipment ought to have an audit trail and be validated to ensure reproducibility within the findings . The positive aspects and disadvantages of model-based approaches from drug discovery on the clinical practice are going to be highlighted from the following paragraphs. M&S in drug discovery In the course of lead optimisation and candidate selection go/no-go decisions have to become made. In the very first step of development of an new molecular entity , absorption, distribution, metabolism and elimination information is required to understand the drug’s properties in vivo . The application of M&S methodologies at this stage will support and facilitate decision-making processes. Predictive models assist the selection of appropriate purchase Tyrphostin 9 candidates, as well as the design of in vivo PK studies . The obvious advantage of this application is the possibility of integrating in vitro to in vivo properties as well as to pharmacodynamic characteristics, identifying differences in drug performance in vivo, as opposed to decision-making based on isolated developability criteria. This concept has been recently applied within the evaluation of COX2 inhibitors . Furthermore, M&S allow optimisation of experimental protocols. At this stage, pharmacokinetics can also be evaluated by studying each part from the ADME approach in an integrated manner. Physiologically-based pharmacokinetic models provide an integrated view of drug disposition in vivo . In contrast to empirical compartmental models, a PBPK model is aimed at describing the in vivo behaviour with the drug before the acquisition of in vivo data. PBPK relies primarily on describing drug disposition in terms of organ Pazopanib distribution, blood flow and metabolic capacity . This allows better understanding of PK properties, more rational candidate selection, and extrapolation of dose levels, of routes of administration, and of data across species. This strategy has some appealing features in that predictions might be made about the need for changes in dosing regimen because of developmental and other agerelated factors . The relevance of this type of information is evident already at the lead optimisation stage: better and quicker understanding of a drug’s PK profile in vivo may drastically improve the decision-making procedure. Nevertheless, it is worth highlighting that the predictive value of these models depends over the selection of correct model parameterisation and about the availability of suitable descriptors . M&S in non-clinical drug development At the non-clinical phase in vitro and in vivo animal studies are the main source of information about pharmacokinetic and pharmacodynamic properties.