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.

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

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

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.

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

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

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

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

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

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

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

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

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.

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

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.

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.

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

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.

An integrated approach of physiological concepts, advanced statistical approaches and large clinical datasets.

Can the (industrial) herbal extraction process be mathematically described and can this model be used to optimize the extraction in terms of quality and economical parameters?

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

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…

We strive to address the challenge of constructing a modeling language to write software which can take advantage of recent hardware developments (multicore, cloud) without compromising in its abstraction levels.

Promotor: Roeland M.H. Merks

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.

This computational approach to the complexity of text comprehension is useful for describing the cognitive processes involved.

Existing work in probabilistic language modeling can be mostly divided into two categories: (i) Purely sequential, string-level approaches ensure fluency at the local level without notion of grammaticality and seek improvements in the use of massive training corpora. (ii) Fully structural, tree-based…

Description of Biotic ligand models: making an inventory of available models & assessment of the variability of the predicted HC5 using the BLMs in different Dutch water types (2005 - 2007)

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

Real-life processes are characterized by dynamics involving time. Examples are walking, sleeping, disease progress in medical treatment, and events in a workflow.

Promotor: Prof.dr. E. Deprettere

PhD Defence

Main challenges in skin vaccination are overcoming the stratum corneum (SC) barrier and targeting the antigen presenting cells (APC) in the epidermis and the dermis.

Promotores: Prof.dr. P.C.W. Hogendoorn & Prof.dr. H.P. Spaink, Co-promotor: Dr. B.E. Snaar-Jagalska

This dissertation studies the Asymptotics of Bayesian nonparametric inference for Gaussian linear models.

Immunotherapies for cancer are an emerging class of therapeutic strategies which aim to treat cancer via augmentation of the immune system.

Industrial manufacturing processes, such as the production of steel or the stamping of car body parts, are complex semi-batch processes with many process steps, machine parameters and quality indicators.

Key publications of the Predictive Pharmacology group.

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.

Science, Leiden Academic Centre for Drug Research (LACDR)

... which build on self-regulation and stress-regulation theories and considers the modification of cognitions as a mediator of therapeutic change.

The molecular mechanisms that instigate a healthy cell to become malignant are fueled by (epi)genetic alterations in so-called driver genes.