Projects
Model-informed precision dosing of tacrolimus in solid organ transplant recipients KU Leuven
Yannick Hofferts works on clinical data analysis as well as on modeling and simulation to improve the dosing of critical medication. He uses computational approaches to create, evaluate, and apply pharmacokinetics and pharmacodynamics models. The overall goal is to predict exposure and therapeutic response in vulnerable patient populations and identify sources of variability among populations to improve pharmacotherapy and, thus, clinical ...
Model-informed drug development: application to drug-induced cholestasis KU Leuven
Drug-induced liver injury (DILI) may impair liver function and lead to liver failure or even fatality, resulting in a considerable burden on the healthcare system. In addition, drug candidates that injure the liver may terminate clinical trials, be disapproved, or be withdrawn from the market, either of which causes appreciable losses for the pharmaceutical companies. To improve drug safety and minimise the attrition during drug development, ...
Computer-assisted dosing recommendation framework, feasibility study and proof of concept implementation for tacrolimus KU Leuven
An overwhelming number of medicinal products are marketed with the same fixed dose for every patient. Adapting the dose for each patient should result in superior efficacy and safety, at least in theory. The gold standard of dosing individualization is model-informed precision dosing (MIPD). An extensive dataset of many patients is used to identify a population pharmacokinetic/pharmacodynamic model (popPK/PD). This is composed of a ...
Mold-active Azoles: Development, Validation and Implementation of strategies for Safe and Effective Dosing (M-ADVISED) KU Leuven
Infections, including severe bacterial infections and invasive fungal infections, are a major cause of morbidity and mortality in critically ill patients and other patient populations (i.e. patients with hematological malignancies). Therapeutic exposure to antibacterial or antifungal drugs at the site of infection (or in plasma as a surrogate matrix) is crucial for successful treatment of severe bacterial and fungal infections. However, it ...
A Pharmacometrics Approach to Improve Dose Individualisation Methods of Biologicals in Patients with Chronic Inflammatory Diseases KU Leuven
In clinical drug development, “one dose fits all” is a key objective. However, variability in exposure and thus response is common and can result in suboptimal treatment of individual patients. To hit a predefined exposure target in each patient, “therapeutic drug monitoring” (TDM) is often implemented. TDM helps improving attainment of a desired exposure target by guiding individualised drug dosing based upon drug concentrations. “Population ...
Joint pharmacometrics modeling of antimicrobial exposure, biomarkers, and clinical outcome assessments to improve the in silico exploration of dose optimization strategies in critically ill patients KU Leuven
Dosage regimens of antimicrobial drugs predominantly stem from in vitro and animal studies. Critically ill patients display altered, highly variable drug concentration-time profiles in their bodies (i.e., pharmacokinetics; PK). Therefore, therapeutic drug monitoring (TDM) has been used to individualize dosing in this vulnerable patient group. TDM guides dosing based on drug concentration measurements, thereby maximizing the chance to meet ...
Master protocol methodological pharmacometrics research KU Leuven
Background and rationale: Pharmacometrics (mixed effects) modelling and simulation is increasingly used to characterise, understand, and predict the dose-exposure-response relationships of drugs. Consequently, model-informed drug development (MIDD) has become an established business value, facilitating a cost-efficient drug development process. Population-level dosing is the preferred dosage strategy, followed by group-level dosing ...
Pharmacometric models for improved therapeutic drug monitoring of ceftriaxone, posaconazole and infliximab KU Leuven
In clinical drug development, “one dose fits all” is a key objective. However, variability in exposure (E) and response (R) is common and can result in suboptimal treatment of individual patients. To hit a predefined E/R target in each patient, “therapeutic drug monitoring” or TDM is often implemented. TDM helps improving attainment of a desired E/R target by guiding individualised drug dosing based upon drug concentrations. “Population ...
Personalized pharmacotherapy in neonates: from (patho)physiology to innovative pharmacokinetic and pharmacodynamic tools KU Leuven
In Flanders 8834 of all 63899 live-born neonates (14%) needed a neonatal or neonatal intensive care unit admission in 2021, because of prematurity, adaptation, critical illness, infections, or congenital malformations. Drugs play a pivotal role in the care of these highly vulnerable patients, but have been introduced without standard regulatory drug development process. Consequently the neonate remains a ‘therapeutic orphan’. Lack of ...