High-throughput holistic preclinical screens are increasingly used in drug discovery, to assess both drug efficacy and drug safety.

The prevalence of obesity (BMI >40 kg/m2) has increased rapidly over the recent years, not only in adults, but also in children and adolescents.

Accurate prediction of the unbound drug concentration-time profile at the CNS target site is crucial for the assessment of the right drug concentration-effect relationship. PBPK models have supported the PK prediction of the CNS target sites and the translation of PK data between species and between…

Promotor: M. Danhof, Co-promotores: J. Freijer, A. Yassen

In this thesis population pharmacokinetic and physiologically-based pharmacokinetic (PBPK) approaches were applied to investigate the influence of glomerular filtration (GF) and active tubular secretion (ATS) on renal clearance in children.

Promotores: C.A.J. Knibbe; J.N. van den Anker, Co-promotores: H.P.A. van Dongen; B. van Ramshorst

The zebrafish is a promising vertebrate model organism in early drug discovery and development.

Clinical development of drugs for central nervous system (CNS) disorders has been particularly challenging and still suffers from high attrition rates.

Discovery and development of Central Nervous System (CNS) drugs is hampered by high attrition rates.

Promotor: C.A.J. Knibbe, Co-promotor: J.J. Boelens, R.G.M. Bredius

Currently, more than 80% of drugs are used in an off-label manner in critically ill neonates.

Prematurely born neonates require, amongst others, pharmaceutical therapy. Dosing guidelines for these therapies are often based on data from term born neonates or older infants, while these are not necessarily similar to prematurely born neonates.

The aim of this thesis is to expedite and ensure the systematic accuracy of clearance scaling from adults to paediatric patients, with a special focus on drugs undergoing hepatic metabolism.

PhD candidates Mohammed Saleh and Berfin Gülave (Division of Systems Pharmacology and Pharmacy) published their research paper on “Using the LeiCNS-PK3.0 Physiologically-Based Pharmacokinetic Model to Predict Brain Extracellular Fluid Pharmacokinetics in Mice”.

Growth and development affect the metabolism of drugs administered to neonates, infants, and children.

The last decades it is increasingly recognized that acute as well as chronic postoperative pain is an important problem. Treatment and prevention of postoperative pain is a challenge, especially in special patient populations where there is only limited guidance on how to optimally use opioids.

Sepsis is a life-threatening condition caused by a dysregulated host response to infection, it is associated with significant morbidity, mortality, and with a high financial burden on global healthcare systems. Bacterial infections are the primary cause of sepsis, but the growing prevalence of antimicrobial…

Promotor: Prof.dr. M. Danhof, Co-promotor: E.C.M. de Lange

Promotores: Prof.dr. C.A.J. Knibbe, Prof.dr. M. Danhof, Prof.dr. K. Allegaert (Leuven)

Promotor: Prof.dr. M. Danhof, Co-promotor: O.E. Della Pasqua

Fungal infections pose a significant threat to individuals with compromised immune systems and despite advancements in diagnosis and treatment, they continue to jeopardize patient’s health.

Antimicrobial drugs constitute a fundamental part of modern medicine. The global rise in antimicrobial resistance poses a major threat to global health.

Growth hormone profiles are pulsatile and highly variable between individuals, limiting the implementation of mathemathical models to quantify an individual's secretion.

Although rarely considered by the pharmaceutical industry or clinicians, 24-hour rhythms in physiology are a factor of potential influence on the pharmacokinetics and pharmacodynamics of drugs.

Clearance is the most important pharmacokinetic parameter for drug dose selection. Pharmacokinetic information is typically first available in the adult population, and in general only limited pharmacokinetic data are available in children when drugs enter into the market. It is therefore of the utmost…

PhD defence

Key publications of the Quantitative Clinical Pharmacology group

Key publications of the Predictive Pharmacology group.

A next, general pharmacological problem to be tackled is how drug-target binding kinetics in vivo, affects target occupancy as an important indicator of the time-course of drug effects.

Prediction of human (CNS) target site concentrations in health and disease In the vision of Prof. de Lange we will only be able to predict human (central nervous system, CNS) target site concentrations and effects if we perform systematic, condition-dependent, integrative, and strictly quantitative…

Tuberculosis causes 1.5 million deaths yearly and anti-tuberculosis therapies are threatened by emergence of drug resistance. Development of innovative drug combinations should be accelerated with the use of translational pharmacological models. Moreover, host-directed therapies (HDT), which stimulate…

Knowledge on how to adjust a drug dose in special patient populations such as (prematurely born) neonates or children, obese individuals or critically-ill patients, is not only crucial for novel compounds, but also for existing drugs which are often used in an off-label manner in these special patient…

This research area is focused on the development and application of novel concepts and models in the emerging area of quantitative systems pharmacology (QSP).

Timely, adequate and optimal treatment of infectious diseases is essential for the survival of patients with bacterial infections (Surviving Sepsis campaign).

An overview of research projects at the Predictive Pharmacology group.

A novel mathematical model describes spatial-temporal drug distribution within one or more brain units, which are cubic representations of a piece of brain tissue with brain capillaries at the edges.

M. Danhof, Co-promotor: O.E. Della Pasqua

After 41 years, Meindert Danhof, Professor of Pharmacology, is leaving the Leiden Academic Centre for Drug Research on 31 March. A symposium in his honour, prior to his farewell lecture, will show what has been achieved in this period. Danhof takes a look back on his career.

The Pharmacy research group focusses on the development of predictive models to improve clinical drug efficacy and safety. We work on clinical problems that require further mechanistic understanding and strive for ultimate benefit to patients.

Are you looking for a research project? We have projects available for motivated 6–9-month internship students with particular interest in organic/polymer synthesis, formulation development, gene delivery, protein delivery, and the preliminairy in vitro screening of drug delivery platforms. Students…

PhD defence

Previous research has found important inter-individual differences in the pharmacokinetics (PK) of morphine in special populations such as children, the morbidly obese or the critically ill.

The lack of success of new CNS drugs in clinical development is in part due to the complexity of the CNS, unexpected side effects, difficulties for drugs to penetrate the brain, but also by the lack of biomarkers.

The overarching clinical aim of this thesis was to improve pharmacological pain management by characterizing the pharmacodynamics of analgesics.

In this thesis, mathematical modeling and simulation was applied as a tool to inform quantitative decision making in oncology drug discovery and development.

The research of the Biotherapeutic Delivery group led by Joachim Van Guyse focuses on developing novel polymer-based formulations for therapeutic nucleic acid and protein delivery. The research revolves around developing structure-activity relationships between the chemical structure of polymers, the…

The list of substances prohibited by the World Anti-Doping Agency (WADA) is huge. PhD candidate Jules Heuberger looked at many of these, as well as at the methods used to detect them. He concluded that for very few of these substances is there is evidence that they actually do enhance performance. PhD…

PhD defence

Prof. Elizabeth de Lange is concerned with the allocation of resources for the conduct of science towards the goal of best serving the public interest. Also, while she underscores that there is still the need for using animals in drug research, she is concerned about this use, and advocates the use…

Data analysis with Python and R are rapidly becoming essential skills for modern scientists. Therefore, we are offering courses to develop your scientific computing skills. Those courses are optional for LACDR PhD candidates.