Therapeutic Drug Monitoring

Suitable drugs for therapeutic drug monitoring (TDM) programs are mainly those with large inter-individual but low intra-individual pharmacokinetic variability, with both consistent concentration–efficacy and/or concentration–toxicity relationships (Ensom et al. 1998): anticancer, immunosuppressive, antibiotic drugs, etc…

Usually, TDM consists of determining a concentration, comparing it to the therapeutic index and adjusting the dose if necessary (i.e. if the concentration falls outside the therapeutic range).

For some drugs, the measured concentration is not sufficiently informative. This is mostly the case when the blood sample is taken at a non conventional sampling time. Thus, an estimation of a specific concentration (i.e. the trough) or of a pharmacokinetic parameter (i.e Area Under the Curve) is needed.
This is possible by applying a population-pharmacokinetic approach.

Anti-Infectious Drugs

Ritonavir-boosted Atazanavir

Atazanavir is a recent Human Immunodeficiency Virus protease inhibitor used as first-line therapy. French Guidelines (Morlat’s report 2013) propose a therapeutic index for the trough concentration. Unfortunately, blood samples are hardly ever taken just before the next drug administration.

Based on two published pharmacokinetic-population models (Dickinson et al. 2009; Schipani et al. 2013) coupled with a Bayesian methodology, we have developed software (IADAv1) (1) to estimate the trough concentration of atazanavir from the measured plasma concentration whenever the sampling time and (2) to propose dose adjustments if necessary to reach concentrations included within the therapeutic index (Morlat’s report 2013). Other softwares for anti-HIV drugs are in the pipeline.

  • Don’t forget to activate the macros and to load the Solver (see “Installation Guide for IADA”) before using IADAv1;
  • IADAv1 is free software exploitable only for patients receiving repeated oral route administration of ritonavir-boosted atazanavir;