This repository contains a methodology to estimate population pharmacokinetic (PopPK) parameters, along with inter-individual variabilities, using only reported patients’ mean plasma concentrations and their standard deviations (SDs) versus time. A Bayesian solution is provided by utilizing virtual patients and using simulation to reconstruct the likelihood of the aggregate data. The method was assessed in R by its application to real data of a 7 mg dosage froup of gevokizumab, a monoclonal antibody, (Cavelti-Weder et al., 2012) to estimate the drug’s PopPK parameters of a second generation minimal Physiologically-Based PK (mPBPK) model. Also, a mixed effects approach was used in RStan to allow accounting for the potential inter-group variability (IGV) among the real data of the five dosage-groups of gevokizumab. It is noteworthy that the method could be applied not only to gevokizumab or monoclonal antibodies in general, but also to a variety of drugs and PK models. To highlight this, a theoretical IV administration of a drug, following a simple one-compartment model was also utilized. This template could be used as a guide when one analyst wishes to apply the proposed methodology to a drug of his/her interest with a more complicated PK model (2- or 3- compartment model), when only aggregate data is available (mean plasma concentrations and their SDs). Developed by the Pharmacometrics group of the Department of Pharmacy of the National Kapodistrian University of Athens (NKUA). Contributors: Evangelos Karakitsios and Aris Dokoumetzidis, (c) 2024. The repository consists of the following:
- As far as our fit for the 7 mg dosage-group is concerned, the related RData file named "ONE_DOSE.RData" is provided. In addition, a “7 mg dosage-group” R file is provided, where after loading the previous RData file the displayed commands can be executed
- Regarding the fit of all five dosage-groups, an R file named “FIVE_DOSES_FIT.R”, as well as a stan file, named “FIVE_DOSES_FIT”. The related RData file “FIVE_DOSES” is also provided.
- Concerning the simple template, two related files, an R file named “iv_bolus” and a Stan file named “iv_bolus”, are provided as well.