This thesis aimed to investigate the impact of exposure dynamics, relative contributions of ENPs(particle) and ENPs(ion), and dosing regimens on the toxicity of ENPs varying in different physico-chemical properties, on the composition and functioning of soil microbial communities.

Promotores: Prof.dr. W.J.G.M. Peijnenburg & Dr. M.G. Vijver

How to make a quantitative assessment of the relative contribution to toxicity of ions and particles? Is the toxicity of nanoparticles related to their size or shape? Which physicochemical property of nanoparticles is an appropriate dose metric of nanoparticles?

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

The path to rational drug and dose selection

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

Promotor: C.A.J. Knibbe, Co-promotores: H.P.A. van Dongen, B. van Ramshorst

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

Leiden researchers have developed an app that doctors can use to more easily determine the right dosage of medication for corona patients. At the moment, doctors are prescribing many existing kinds of medication to patients. Using the app, they can determine a safe and effective dosage.

Although nanoparticles are extensively used in various applications like consumer products and have most probably entered the environment, little is known about the effects of these particles on living organisms.

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

Childhood obesity is an increasing health issue. In the first part of this thesis comorbidities in children with obesity were studied, concerning the diagnostic process and dosing regimens.

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…

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.

Transcutaneous vaccination is attractive because it is non- or minimally invasive, pain free and the site of administration (skin) is easily accessible. What’s more, transcutaneous immunization can lead to a strong immune response owing to the presence of immune-competent cells in the skin.

Systems pharmacology aims to apply techniques from systems biology to pharmacological models.

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

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.

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

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 Quantitative Clinical Pharmacology group

PhD Defence

Mouse models are commonly used to assess the immunogenicity of therapeutic proteins and to investigate the immunological processes leading to antidrug antibodies. The aim of this work was to develop a transgenic (TG) Balb/c mouse model for evaluating the immunogenicity of recombinant human insulin (insulin)…

Microneedle-based vaccination has several advantages over vaccination by using conventional hypodermic needles.

Traditionally, vaccines are administered intramuscularly using conventional hypodermic needles, which cause pain and distress. Microneedles are very short needles (smaller than 1 mm) that are practically invisible to the naked eye.

The Quantitative Clinical Pharmacology group is led by Prof. Dr. Catherijne Knibbe. Her research group aims to define how to adjust a drug dose in special patient populations such as (prematurely born) neonates or children, obese individuals or critically ill patients. Through combining the statistical…

Ecotox is a stimulating top-facility that provides an integrative research environment around the topic of ecotoxicological testing and experimental research. Research focus: Dose-response modelling Mode-of-actions and mechanism-of-actions Test method development, in view of targets in…

The Quantitative Pharmacology group headed by Coen van Hasselt focusses on the application of state-of-the-art quantitative pharmacological mathematical and statistical (pharmacometrics) modeling combined with systems biology modeling approaches, to characterize biomarkers for of disease and treatment…

PhD Defence

This paper describes two synthetic lipid models designed to replace human stratum corneum (SC) in studies of the impact of volatile organic chemicals on the molecular organization of the skin barrier lipids.

Promotor: Jan van der Greef; Co-promotors: Mei Wang; Eduard van Wijk

Source: Nat Biotechnol, Volume 32, Issue 12, pp. 1213-22 (2014)

Electron microscopy has become an extremely important techniquein a wide variety of elds.

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

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

Adverse drug reactions (ADRs) remain one of the major reasons for patient mortality and (early) drug withdrawal. Currently, different in vivo and in vitro models are used to assess the toxic potential of drugs in the pre-clinical phase. Unfortunately, the predictive value of this model does not fit…

Promotor: Prof.dr. J.P. Abrahams, Prof.dr. M. van Heel

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

Promotor: Prof.dr. K.J. Batenburg

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

How do nanoparticles bioaccumulate and biodistribute in organisms?

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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.

PhD Defence

How can we implement the technique of pharmacological resting-state fMRI to improve the diagnosis of dementia?

Large parts of the research described in this Thesis aims at the development of oligopeptide-masked toxins and their in situ immunoproteasome-mediated activation.

Pharmacogenetics is nowadays increasingly incorporated in the clinic to better predict pharmacokinetics and optimize dosing regimens of drug treatments. While this approach has been successful and improved our prediction of drug metabolism, drug levels within patients may still commonly deviate between…

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

Doctors and pharmacists should take greater account of obesity when dosing medicines. The distribution in the body and the breakdown of a medicine can vary considerably in obese patients. This is stated by clinical pharmacologist Catherijne Knibbe in the Annual Review of Pharmacology and Toxicology.

Former masterstudent Bio-Pharmaceutical Sciences Maddalena Centanni will be awarded the 2020 Arenberg Coimbra Prize for Erasmus Students. Centanni spent her six month Erasmus exchange at Uppsala Universiy in Sweden where she looked for ways to improve anti-cancer drug dosing.