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

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

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

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

In neonates and infants, body size, enzyme pathways, and expression and function of receptors and (target) proteins are still developing.

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.

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.

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.

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

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

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

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

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

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.

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.

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

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.

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…

Key publications of the Predictive Pharmacology group.

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

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

The Systems Pharmacology group is headed by Prof. Piet Hein van der Graaf. Systems Pharmacology is the quantitative analysis of the dynamic interactions between drugs and a biological system to understand the behaviour of the system as a whole, as opposed to the behaviour of its individual constituents;…

PhD defence

PhD defence

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.

Key publications of the Systems Pharmacology group

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.

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

Promotor: Prof.dr. M. Danhof, Co-Promotor: J. de Jongh

Animal Sciences’ contribution to the Bioactive Molecules research theme includes research on molecules from natural sources, such as plants, insects, and snake venom, with the aim to identify novel anti-cancer, anti-inflammatory, anti-microbial, and anti-diabetic agents.

Key publications of the Analytical BioSciences and Metabolomics group

The Minor Computational Approaches to Disease, Signaling and Drug Targets (CADSDT) is focused on fundamental scientific research required for discovery of new drug targets and development of new drugs.

This book describes the different approaches for drug delivery to the brain with an emphasis on the physiology of the blood-brain barrier (BBB) and the governing principles and concepts for drug delivery across the BBB

The Pharmacy research group focusses on the development of predictive models to improve clinical drug efficacy and safety. We are moreover strongly involved in the Master specialisation of Pharmacy at Leiden University. We work on clinical problems that require further mechanistic understanding and…

An important hormone excreting gland in the human body is the pituitary

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.

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

An overview of research projects at the Predictive Pharmacology group.

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.

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

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…

We aim to gain a better understanding of the natural disease progression of ALS in order to improve clinical trial design and analysis and to support drug discovery and clinical development of new drugs.

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

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…

Key publications of the Quantitative Clinical Pharmacology group

Krekels received both the Thesis Award and the TOP Publication Award for her thesis 'Size does matter: drug glucuronidation in children'. Her research led to a new dosage regimen of morphine for babies and toddlers. Both prizes were awarded during the scientific meeting of the NVKFB on Friday 11 Apr…

Professor of Predictive Pharmacology Elizabeth de Lange has received an Honorary Doctorate from the Faculty of Pharmacy of Uppsala University. She will be honoured during the Uppsala Winter Conferment Ceremony on 31 January 2020.