About our research group/lab
dr. Birgit CP Koch leads this research group of ten PhD students (three finished), three postdoc and three research technicians. The focus of the group is on pharmacokinetics (PK) and pharmacodynamics (PD), Therapeutic Drug Monitoring (TDM), and the implementation of these research areas in clinical practice.
No two patients are identical, so individual drug dosing can lead to better treatment. This groups uses a PK/PD model to establish the relationship between drug dosage, drug concentration and drug effect. During the last ten years, they have organised the structure of the PK/PD and TDM laboratory and the PK/PD research group to conduct model-based dosing and bio-analysis, andimplement results in clinical practice. They use (non)compartmental (non-linear mixed) modelling to build the PK/PD models.
Targets for the future
From 'one dose fits all' to 'one dose fits one'
When it comes to traditional TDM and PK/PD and Model-based Dosing, pharmacotherapy is increasingly moving from a 'one size fits all' approach to personalised medicine (or precision medicine). Genetic information (germline DNA and tumour DNA) plays an important role in explaining between patient variability in drug response. However, the efficacy and toxicity of drug treatment can vary substantially even within groups of patients with the same genetic background. We are therefore integrating PK/PD and TDM in research and clinical patient work.
Our laboratory has a track record in assay development. TDM is increasingly combined with Model-based Dosing. Population pharmacokinetic (PK) models aim to explain variability in pharmacokinetics through covariates such as body weight, age, renal function and co-medication. The use of iterative Bayesian methods to analyse individual patient data can help to define a dose recommendation with the highest likelihood of reaching the target concentration. Acceptance of Bayesian models for TDM is now increasing. The integration of outcome measures allows for PK/PD modelling, also referred to as pharmacometrics.
PK/PD modelling mathematically expresses the time course of the biological effect in response to drug concentration. To assess exposure/response relationships, a variety of PK/PD tools are currently being investigated (including target-mediated disposition models, allometric scaling and physiologically-based PK models. Investing in this part of our research will allow us to apply our existing expertise to different fields.
In addition, we will develop real-time TDM together with technical universities and infection site measurements will be a new technique. Alternative matrices in general (as well as dried blood spots) will be covered in this research line.
Dr. Birgit Koch will lead this line. She was recently appointed as the new medical coordinator for research and teaching.
- Pipamperone Population Pharmacokinetics Related to Effectiveness and Side Effects in Children and Adolescents.
Kloosterboer SM, Egberts KM, de Winter BCM, van Gelder T, Gerlach M, Hillegers MHJ, Dieleman GC, Bahmany S, Reichart CG, van Daalen E, Kouijzer MEJ, Dierckx B, Koch BCP.Clin Pharmacokinet. 2020 May 11. doi: 10.1007/s40262-020-00894-y. Online ahead of print.PMID: 32394297
- Pharmacokinetic modeling of intravenous sildenafil in newborns with congenital diaphragmatic hernia.
Cochius-den Otter SCM, Kipfmueller F, de Winter BCM, Allegaert K, Tibboel D, Mueller A, Koch BCP.Eur J Clin Pharmacol. 2020 Feb;76(2):219-227. doi: 10.1007/s00228-019-02767-1. Epub 2019 Nov 18.PMID: 31740991
- Psychotropic drug concentrations and clinical outcomes in children and adolescents: a systematic review.
Kloosterboer SM, Vierhout D, Stojanova J, Egberts KM, Gerlach M, Dieleman GC, Hillegers MHJ, Passe KM, Gelder TV, Dierckx B,Koch BCP.Expert Opin Drug Saf. 2020 May 18. doi: 10.1080/14740338.2020.1770224. Online ahead of print.PMID: 32421365
- Population pharmacokinetics and target attainment of ciprofloxacin in critically ill patients.
Eur J Clin Pharmacol. 2020 Jul;76(7):957-967. doi: 10.1007/s00228-020-02873-5. Epub 2020 Apr 19.PMID: 32307575
- Simultaneous quantification of ambrisentan, macitentan and sitaxentan in human plasma using UPLC-MS/MS.Biomed Chromatogr. 2020 Mar;34(3):e4787. doi: 10.1002/bmc.4787. Epub 2020 Jan 19.PMID: 31875652
- A Population Pharmacokinetic Model Does Not Predict the Optimal Starting Dose of Tacrolimus in Pediatric Renal Transplant Recipients in a Prospective Study: Lessons Learned and Model Improvement.
Andrews LM,de Winter BCM, Cornelissen EAM, de Jong H, Hesselink DA, Schreuder MF, Brüggemann RJM, van Gelder T, Cransberg K.Clin Pharmacokinet. 2020 May;59(5):591-603. doi: 10.1007/s40262-019-00831-8.PMID: 31654367
- Clinical implications of food-drug interactions with small-molecule kinase inhibitors.
Lancet Oncol. 2020 May;21(5
- Intratumoral Comparison of Nanoparticle Entrapped Docetaxel (CPC634) with Conventional Docetaxel in Patients with Solid Tumors.
Clin Cancer Res. 2020 Apr 22. doi: 10.1158/1078-0432.CCR-20-0008. Online ahead of print. PMID: 32321718
Dr. R.B. Flint
Dr. B.C.P. Koch
Principal Investigator, Associate Professor
Dr. S.L.W. Koolen
Hospital Pharmacologist - Clinical Pharmacologist
Dr. F. van Rosse
Dr. J. Versmissen
Assistant Professor, PI
Dr. B.C.M. de Winter
PhD, PharmD, Assistant Professor