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

Course

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

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

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

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

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

Pharmacokinetic studies in obese adolescents and obese adults

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.

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

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

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

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

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

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

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.

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

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.

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

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…

The brain is a complex organ, and researching medicine to treat brain disorders is equally if not more complex. Elizabeth (Liesbeth) de Lange, Professor of Predictive Pharmacology, calls for a structured approach. ‘In effect, it's like playing Mastermind.’ Inaugural lecture on 22 March.

PhD Defence

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

PhD Defence

PhD Defence

In order to better understand the course of Alzheimer’s disease, Frédérique Kok believes that a strategic and structured approach is needed: the Mastermind research approach. With her LUF grant, Kok wants to generate high-quality data to build a mathematical model that can recognize the onset of the…

PhD Defence

PhD Defence

PhD Defence

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…

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

Key publications of the Predictive Pharmacology group.

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

Key publications of the Quantitative 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.

The kidneys play a major role in the elimination of drugs. In children, the exact age-related physiological changes underlying kidney function remain largely unknown.

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

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…

The Institute of Biology Leiden (IBL) is an internationally oriented institute for research and education in biology. We are part of the Faculty of Science at Leiden University.

Oxidation is a common degradation pathway that affects therapeutic proteins and peptides during production, purification, formulation, transportation, storage and handling of solid and liquid preparations. In the present work we review the scientific literature about structural and biological consequences…

Key publications of the Quantitative Clinical Pharmacology group

The cannabinoid CB2 receptor (CB2R) represents a promising therapeutic target for various forms of tissue injury and inflammatory diseases. Although numerous compounds have been developed and widely used to target CB2R, their selectivity, molecular mode of action and pharmacokinetic properties have…

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;…

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.

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