HT23
Background: Tuberculosis (TB), caused by Mycobacterium tuberculosis, is one of the most common causes of death due to a single infectious agent, with about 10 million new cases and 1.5 million deaths in 2020 globally [1], surpassed only by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) in 2020. The treatment success rate for new and recurrent TB cases treated with first-line regimens was estimated at 86% globally in 2019, and only 59% for drug-resistant TB [1]. This means that a substantial number of patients fail to respond to treatment, have a relapse of disease or develop drug-resistant TB [1]. There are multiple reasons for an unsuccessful treatment outcome such as suboptimal plasma concentrations of TB drugs.
A strategy to avoid insufficient plasma concentrations and therefore enhance cure rates is individualized dosing. By measuring an individual’s drug exposure and adjusting the patient’s dose using mathematical modelling, individualized dosing is a tool to personalise treatment and thereby achieve the best possible treatment response [2]. Standardization of processes for individualized dosing is important in order to ensure high quality dosing recommendations.
Aim: The objective of this project is to develop a standardized workflow for model-based individualized dosing of anti-tuberculosis drugs.
Method: You will be working with “NONMEM”, a software for nonlinear mixed-effects modelling and “R”. Data from clinical trials and simulations will be used. A population PK model will be used.
References:
[1] Global tuberculosis report 2021. World Health Organization; 2021. License: CC BY-NC-SA 3.0 IGO.
[2] Van Beek SW et al. Personalised tuberculosis treatment through model informed dosing of rifampicin. Clin Pharmacokinet. https://www.ncbi.nlm.nih.gov/pubmed/30671890 (2019).
Farmaceutisk vetenskap
Biofarmaci
Beräkningsstudie
Uppsala University
Uppsala
Lina Keutzer och Ulrika Simonsson
lina.keutzer@farmbio.uu.se
Institutionen för farmaceutisk biovetenskap
Apotekarprogrammet
Fördjupningsprojekt i biofarmaci 30 hp - 3FG008
30hp
1