[Biomarkers and pharmacokinetic-pharmacodynamic studies of immunosuppressive agents].

Biomarkers are characteristics that are objectively measured and evaluated as indicators of normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention. Biomarkers of pharmacological responses allow pharmacokinetic-pharmacodynamic modelling based on what is known of the mechanism of action of the drug. Characteristics predictive of the pharmacological response, such as a genotype, constitute a specific category of biomarkers and can be used as covariates in the model. In the case of "classical" immunosuppressive agents, the biomarkers of response most studied are lymphocyte calcineurin activity for ciclosporin and tacrolimus, and inosine monophosphate dehydrogenase activity for mycophenolate. Pharmacokinetic-pharmacodynamic analysis of monoclonal antibodies with immunosuppressive properties requires complex models and immunological biomarkers such as, for example, the number of circulating lymphocytes with a given surface antigen. Pharmacodynamic indirect response models are particularly relevant in this instance.