Population pharmacokinetics in patients with infectious diseases

• Grant number: 22/09254-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): August 01, 2022
• Effective date (End): July 31, 2024
• Field of knowledge: Biological Sciences - Pharmacology - Clinical Pharmacology
• Principal Investigator: Vera Lúcia Lanchote
• Grantee: Tiago Antunes Paz
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 18/05616-3 - Clinical pharmacokinetics in infectious diseases, AP.TEM

Abstract

The thematic project called Clinical pharmacokinetics in infectious diseases brings together 06 subprojects of relevance in precision medicine. Subprojects 1, 3 and 6 cover the development of population pharmacokinetic (popPK) models, which generate estimates of the inter-individual variability of pharmacokinetic parameters, as well as evaluate the effect of individual characteristics, such as weight and other demographic characteristics, genotype, phenotype, co-medication, co-morbidities, among others, allowing a better characterization of an individual in the population through estimates with clearer clinical significance. The popPK models will be developed as non-linear hierarchical mixed effects models using the NONMEM (NonLinear Mixed Effects Modeling) program. Models will be developed based on the decay of plasma concentrations or cerebrospinal fluid concentrations of drugs and/or their metabolites as a function of time, as well as specific data from the literature. The program R: A Language and Environment for Statistical Computing will be used for the reorganization of the data set, statistical analysis and the elaboration of visual diagnostic graphs of the model. Final population pharmacokinetic models should show acceptable predictive performance to describe drug exposure based on quality of fit, bootstrap results, visual predictive verification and NPDE (Normalyzed Prediction Distribution Errors) and mirror plots. Subsequently, secondary parameters will be presented, including absorption rate constant (Ka), total clearance (CL), inter-compartmental clearance (Q), central volume of distribution (Vc), peripheral volume of distribution, among others. (AU)