HT23
Tuberculosis (TB) is an infectious disease that has given rise to the largest number of deaths in history. One major problem associated with TB is treatment failure due to strains of Mycobacterium tuberculosis that are resistant to first line anti-TB drug therapy. In order to combat drug-resistant TB, researchers are developing new anti-TB drugs but there are also drugs which are repurposed.
Linezolid, originally a synthetic antibiotic agent used for gram-positive bacteria, has been repurposed for TB treatment. Linezolid is believed to be a promising anti-TB candidate, as it has no cross-resistance with other anti-TB drugs. However, linezolid has been reported to give rise to adverse reactions such as myelosuppression, thrombocytopenia and peripheral neuropathy. In order to mitigate the toxicity limitations of linezolid, a computational technique, called model-informed precision dosing (MIPD), has been suggested to be used. MIPD can be used to predict individualized doses based on observed individual drug concentrations, patient characteristics and an underlying pharmacokinetic (PK) model in the purpose of reaching effective and safe drug concentrations. For this, the sampling design needs to be optimized to maximize the use of information when individualizing the dose using MIPD in the clinic.
Aim
The aim of this computational project is to optimize the sampling design for linezolid to be used in model-informed precision dosing.
Methods
A previously-developed population pharmacokinetic (popPK) model that describes the PK of linezolid will be used in this analysis. The number and timepoints of samples taken to inform the model will be optimized using the NONMEM software. Dataset building as well as all graphical visualization will be performed in R.
Farmaceutisk vetenskap
Analytisk farmaceutisk kemi
Beräkningsstudie
Uppsala University
Uppsala
Rami Ayon Alsoud och Ulrika Simonsson
rami.alsoud@farmbio.uu.se
Institutionen för farmaceutisk biovetenskap
Apotekarprogrammet
Fördjupningsprojekt i biofarmaci 30 hp - 3FG008
30hp
1