96 search results for “pharmacokinetics” in the Public website
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Systems pharmacology-based translational drug pharmacokinetics
High-throughput holistic preclinical screens are increasingly used in drug discovery, to assess both drug efficacy and drug safety.
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Shaping the pharmacokinetic landscape for renally cleared antibiotics in obesity
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.
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clinical studies in special populations: towards semi-physiological pharmacokinetic models
Promotor: M. Danhof, Co-promotores: J. Freijer, A. Yassen
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The impact of obesity on the pharmacokinetics of drugs in adolescents and adults
Promotores: C.A.J. Knibbe; J.N. van den Anker, Co-promotores: H.P.A. van Dongen; B. van Ramshorst
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renal clearance in children using population pharmacokinetic and physiology based pharmacokinetic modeling approaches
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.
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Translational pharmacokinetics-pharmacodynamics in zebrafish: integration of experimental and computational methods
The zebrafish is a promising vertebrate model organism in early drug discovery and development.
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Individualized dosing of serotherapy in allogeneic hematopoietic cell transplantation - a delicate balance
Promotor: C.A.J. Knibbe, Co-promotor: J.J. Boelens, R.G.M. Bredius
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Systems pharmacokinetic models to the prediction of local CNS drug concentrations in human
Clinical development of drugs for central nervous system (CNS) disorders has been particularly challenging and still suffers from high attrition rates.
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Multi-Biomarker Pharmacokinetic-Pharmacodynamic Relationships of Central Nervous Systems Active Dopaminergic Drugs
Discovery and development of Central Nervous System (CNS) drugs is hampered by high attrition rates.
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Population PKPD analysis within the “DINO-Trial” evaluating the pharmacokinetics and pharmacodynamics of routinely used off-label drugs in premature
Currently, more than 80% of drugs are used in an off-label manner in critically ill neonates.
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How to scale clearance from adults to children for drugs undergoing hepatic metabolism?
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.
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First-pass and systemic metabolism of cytochrome P450 3A substrates in neonates, infants, and children
Growth and development affect the metabolism of drugs administered to neonates, infants, and children.
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Does it still hurt?
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.
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Prediction of brain target site concentrations on the basis of CSF PK: impact of mechanisms of blood-to-brain transport and within brain distribution
Promotor: Prof.dr. M. Danhof, Co-promotor: E.C.M. de Lange
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Towards a system-based pharmacology approach to predict developmental changes in renal drug clearance in children
Promotores: Prof.dr. C.A.J. Knibbe, Prof.dr. M. Danhof, Prof.dr. K. Allegaert (Leuven)
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Pharmacology based toxicity assessment: towards quantitative risk prediction in humans
Promotor: Prof.dr. M. Danhof, Co-promotor: O.E. Della Pasqua
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Quantitative pharmacology of antimicrobials
Antimicrobial drugs constitute a fundamental part of modern medicine. The global rise in antimicrobial resistance poses a major threat to global health.
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Population Pharmacokinetic Modeling
Course
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Catherijne Knibbe
Science
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Population Pharmacokinetic Modeling
Course
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Elizabeth (Liesbeth) de Lange
Science
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From descriptive to predictive pharmacology in children using semi-physiological population modelling: application to hepatic metabolism
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…
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24-hour rhythms in drug exposure and effect
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.
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The quantification of growth hormone secretion : application of model-informed drug development in acromegaly
Growth hormone profiles are pulsatile and highly variable between individuals, limiting the implementation of mathemathical models to quantify an individual's secretion.
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Key publications
Key publications of the Quantitative Clinical Pharmacology group
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Key publications
Key publications of the Predictive Pharmacology group.
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Key publications
Key publications of the Systems Pharmacology group
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Drug-target binding kinetics in vivo
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.
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Individualized dosing of aminoglycosides and glycopeptide antibiotics in (morbidly) obese patients (AMIGO)
Timely, adequate and optimal treatment of infectious diseases is essential for the survival of patients with bacterial infections (Surviving Sepsis campaign).
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Prediction of human (CNS) target site concentrations in health and disease
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…
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Research
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…
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Quantitative Systems Pharmacology
This research area is focused on the development and application of novel concepts and models in the emerging area of quantitative systems pharmacology (QSP).
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Research projects
An overview of research projects at the Predictive Pharmacology group.
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Founding father of pharmacological models
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.
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Novel pharmacometric techniques to quantify the pharmacodynamics of analgesics
The overarching clinical aim of this thesis was to improve pharmacological pain management by characterizing the pharmacodynamics of analgesics.
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Vision
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.
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From data to models: reducing uncertainty in benefit risk assessment: application to chronic iron overload in children
M. Danhof, Co-promotor: O.E. Della Pasqua
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Prediction of spatial-temporal brain drug distribution with a novel mathematical model
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.
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Tamoxifen pharmacogenetics and pharmacokinetics in early-breast cancer
PhD defence
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Shaping the pharmacokinetic landscape for renally cleared antibiotics in obesity
PhD defence
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Treosulfan pharmacokinetics and dynamics in pediatric allogeneic stem cell transplantation
PhD defence
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Pharmacodynamics of analgesics and sedatives in neonates and infants
In neonates and infants, body size, enzyme pathways, and expression and function of receptors and (target) proteins are still developing.
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Systems pharmacology-based optimization of postoperative morphine treatment
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.
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Pharmacometabolomics; prediction of system-wide multi-biomarker drug response
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.
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renal clearance in children using population pharmacokinetic and physiology based pharmacokinetic modeling approaches
PhD defence
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Quantitative systems pharmacology modeling of biotherapeutics in oncology
In this thesis, mathematical modeling and simulation was applied as a tool to inform quantitative decision making in oncology drug discovery and development.
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Little proof that doping really works
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…
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Bioactive Molecules in Animal Sciences
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.
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Cytochrome P450 3A-mediated first-pass and systemic drug metabolism in children
From descriptive to physiological models that can predict oral absorption and elimination of CYP3A substrates across the pediatric age range.
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Quan/Qual analysis of drugs and metabolites in biological matrices
Can we develop a generic method for Quan/Qual analysis of small molecule drugs, their metabolites and endogenous metabolites in (pre-)clinical samples?