This ACE represents the full spectrum of drug research, starting with basic pharmacology, continuing in phase I-IV clinical trials and ending at pharmaco-epidemiology. Integrated diagnostic services (therapeutic drug monitoring, pharmacogenetics) contribute to patient care and drug research.
We provide consultative services, aiming at supporting prescribers in evidence based individualization of cost-effective, safe and affordable drug treatment, or provide evidence for dosing in cases where such evidence is lacking (e.g. children, off-label or unlicensed use). Teaching involves medical students and residents, as well as PhD projects and summer schools. Our aim is to expand existing partnerships and initiate new collaborations.
Research Activities
Our ACE is active in all 4 dimensions (fundamental, translational, clinical and epidemiological research). Given the size of our ACE the projects listed form a small selection.
Translational&Clinical : the group of Danser has a research line in cardiovascular pharmacology. Recently, this has led to several clinical collaborations, such as cardiovascular side-effects of angiogenesis inhibitors (Mathijssen) and preeclampsia (Prof. Steegers). The group in Sophia Childrens Hospital has an long lasting collaboration with LACDR for implementation of model based drug dosing and randomized controlled trials in critical ill children. Epidemiological&Clinical: Stricker focuses on pharmacogenetics and elderly using data from the Rotterdam cohort.
Sturkenboom has a focus on re-use of (global) electronic health care data to study the effects of small molecules and vaccines to support clinical and regulatory decision making. Van den Bemt specializes in medication safety. Koopmanschap is a leading researcher in health technology assessment and pharmacoeconomics. In the Hospital Pharmacy a strong research line in PK/PD and TDM of immunosuppressants, antibiotics (Mouton) and antipsychotics is ongoing (Koch). Existing (inter-)national research collaborations will be intensified. The current interest in personalized medicine fits very well with the expertise available within this ACE. TDM and pharmacogenetics are important tools to individualize drug treatment.
Collaborations
Contributions
The coordinators on education are Danser and Vulto. This includes teaching of basic pharmacological principles, and education in rational pharmacotherapy.
There is a strong involvement in the Research Master Infection & Immunity (van Gelder, van Schaik) and the highest scoring Research Minor: Oncology (Clinical Pharmacology by Mathijssen and Pediatric Oncology by Zwaan). Further contributions to the Molecular Medicine School programs Molecular Biology, SNP-course and the NIHES Summerschool (van Schaik: Pharmacogenetics).
The nationwide COIG-course Clinical Pharmacology is coordinated by van Gelder. Van den Bemt is participating in the new master study for pharmacists in Leiden. Pediatric Pharmacology teaching in the national pediatric residency program is coordinated by Hanff and Allegaert, of the group of Tibboel. Extensive international teaching in Pharmacoepidemiology and Pharmacovigilance is given as part of the Erasmus Summer Program, Erasmus Winter Program, and two joint MSc/PhD programs: the program in Pediatric Medicines Research developed by the Global Research in Pediatrics network for Excellence (Sturkenboom, van den Anker, Verhamme) and the joint EU2P program (Sturkenboom, Verhamme, Stricker).
As part of the Netherlands Institute of Health Sciences, MSc, DSc, and MSc-programs are organized. Pharmacology and drug development is part of several courses of the Molecular Medicine School such as 'Biology of Disease'.
Care Activities
The ACE "Pharmacology & Therapeutics" has an extensive involvement in patient care, especially with respect to diagnostic services (TDM laboratory Hospital Pharmacy / laboratory Translational Pharmacology Medical Oncology, Pharmacogenetics Expert Center, Pediatric Oncology diagnostic laboratory) and medication safety. Clinical Pharmacology is providing consultative services (the "pharmacophone") and an out-patient clinic "Clinical Pharmacology".
Clinical cases are discussed weekly during a clinical pharmacology meeting, and monthly in toxicology meeting, involving all disciplines. The main goal is supporting prescribers in evidence based individualization of safe, affordable, and cost-effective drug treatment, and to provide evidence for pediatric dosing in cases where such evidence is lacking (e.g. off-label or unlicensed use, formulation issues, etc).
Almost 100% of our care is academic. In our activities we assess the traditional outcomes efficacy and safety, (e.g. early clinical trials; phase I/II), and add patient relevant medical outcomes (and thus contribute to Value Based Health Care). Our care is highly innovative with much interest from health insurance, government and industry. The several disciplines in our ACE operate under accredited conditions, such as ISO15189 (Pharmacogenetics Expert-Center Dept. Clinical Chemistry) or CCKL (Pharmacy Laboratory).
Societal Relevance to Research, Education and Patient Care
Individualization of drug treatment is one of the main targets of personalized medicine. This ACE is strongly involved in PK/PD, TDM and pharmacogenetics, and has a long standing tradition in supporting prescribers in selection of drugs or drug doses. The societal relevance of this ACE is therefore high.
Knowledge based on drug-drug interaction studies will be implemented in new guidelines. It will also be used to develop new therapies, making use of synergistic effects, or to create 'smart' solutions to prevent side-effects. Members of our ACE have been actively involved in the Pharmacogenetics Working Group of the Royal Dutch Association for the Advancement of Pharmacy (KNMP). TDM of novel (oral) oncological drugs is becoming reality, and this ACE will take the lead in developing this treatment regimen in daily oncological practice in the Netherlands, and worldwide. This also applies for TDM in alternative matrices.
The Nederlands Kenniscentrum voor Farmacotherapie op de Kinderleeftijd (NKFK) is guided by senior clinicians within this ACE. Health care data generated in the hospital can be transformed into knowledge using epidemiological methods. Membership of the advisory board of Lareb is covered. We are also represented in the boards of the Dutch Society of Hospital Pharmacists, and Dutch Society for Clinical Pharmacology and Biopharmacy.
Viability of Research, Education and Patient Care
This ACE increases the viability of research, education and patient care. Members of our ACE are working in all disciplines, and are relatively young. Our ACE has shown the potential for attracting new people, like students, basic scientists, medical doctors and pharmacists.
So far, every PhD student that participated in our ACE is now working in a related topic (like a medical discipline, or (international) industry), creating a huge network for our ACE potentiating further collaborations and innovative potential. Knowledge sharing is done in the yearly pharmacology research meeting, the weekly pharmacology meeting and the yearly Sophia Research day. International and national conferences are organized by our group to increase viability. Talent identifications via Veni/Mrace and development programs in the hospital such as FCD.
Key and relevant publications of the last five years
- Kang HJ, Loftus S, Taylor A, DiCristina C, Green S, Zwaan CM. Aprepitant for the prevention of chemotherapy-induced nausea and vomiting in children: a randomised, double-blind, phase 3 trial. Lancet Oncol. 2015;16:385-94.
- Lahousse L, Verhamme KM, Stricker BH, Brusselle GG. Cardiac effects of current treatments of chronic obstructive pulmonary disease. Lancet Respir Med 2016;4:149-64.
- van Leeuwen RW, van Gelder T, Mathijssen RH, Jansman FG. Drug-drug interactions with tyrosine-kinase inhibitors: a clinical perspective. Lancet Oncol. 2014;15:e315-26.
- Van der Veldt AA, Eechoute K, Gelderblom H, Gietema J, Guchelaar HJ, van Erp NP, van den Eertwegh AJM, Haanen JB, Mathijssen RH, and Wessels JA. Genetic polymorphisms associated with a prolonged progression-free survival in patients with metastatic renal cell cancer treated with sunitinib. Clin. Cancer Res. 17: 620-629, 2011
- Van Leeuwen RW, Peric R, Hussaarts KG, Kienhuis E, IJzerman NS, de Bruijn P, van der Leest C, Codrington H, Kloover JS, van der Holt B, Aerts JG, van Gelder T, and Mathijssen RH. Influence of the acidic beverage cola on the absorption of erlotinib in patients with non-small-cell lung cancer. J. Clin. Oncol. 34: 1309-1314, 2016.
- JJ Swen, M Nijenhuis, A de Boer, L Grandia, Anke-Hilse Maitland‐van der Zee, H Mulder, GAPJM Rongen, RHN Schaik, T Schalekamp, DJ Touw, J Weide, B Wilffert, VHM Deneer, H‐J Guchelaar Pharmacogenetics: from Bench to Byte – an update of guidelines. Clin Pharmacol Ther 2011;89:662-73.
- Ceelie I, De Wildt SN, Van Dijk M, Van den Berg MMJ, Van den Bosch GE, Duivenvoorden HJ, De Leeuw TG, Mathot R, Knibbe CAJ, Tibboel D. Effect of intravenous paracetamol on postoperative morphine requirements in neonates and infants undergoing major non cardiac Surgery. JAMA 2013:309;149-154.
- Vet NJ, de Wildt SN, Verlaat CW, Knibbe CA, Mooij MG, van Woensel JB, van Rosmalen J, Tibboel D, de Hoog M. A randomized controlled trial of daily sedation interruption in critically ill children. Intensive Care Med. 2015 Nov 24. [Epub ahead of print)
- Durik M, Kavousi M, van der Pluijm I, Isaacs A, Cheng C, Verdonk K, Loot AE, Oeseburg H, Musterd-Bagghoe U, Leijten F, van Veghel R, de Vries R, Rudez G, Brandt R, Ridwan YR, van Deel ED, de Boer M, Tempel D, Fleming I, Mitchell GF, Verwoert G, Tarasov KV, Uitterlinden A, Hofman A, Duckers HJ, van Duijn CM, Oostra BA, Witteman JCM, Duncker DJ, Danser AHJ, Hoeijmakers JH, Roks AJM. Nucleotide excision DNA repair is associated with age-related vascular dysfunction. Circulation 2012;126:468-478.
- Roksnoer LCW, van Veghel R, de Vries R, Garrelds IM, Musterd-Bhaggoe UM, Friesema ECH, Leijten FPJ, Poglitsch M, Domenig O, Hoorn EJ, Danser AHJ, Batenburg WW. Optimum AT1 receptor-neprilysin inhibition has superior cardioprotective effects compared with AT1 receptor blockade alone in hypertensive rats. Kidney Int 2015;88:109-120.
PhD theses of the last five years
- Lisette Binkhorst. Tamoxifen Pharmacokinetics beyond the genotyping era. (24 april 2015)
- Roelof van Leeuwen. Drug-drug interactions in patients treated with anti-cancer agents. (22 april 2016)
- Jacqueline Kloth. Pharmacokinetics and pharmacodynamics of tyrosine kinase inhibitors (1 juli 2015) (1 juli 2015)
- Anne-Joy de Graan. A pharmacological approach to personalize the use of anti-cancer drugs. (20 september 2013)
- Miriam G Mooij. Evolution in pediatric pharmacology. Microdosing, Metabolism and Membrane Transporters. March 30, 2016.
- Nienke Vet. Drug therapy in critically ill children. Are you awake? April 5, 2016
- Botden IPG. Red wine polyphenols and vascular function. May 9, 2012
- te Riet, L. Renin-angiotensin system and genetic factors in aneurysms. A translational approach. April 5, 2016
- Nicolaas Aarts. Utilization and unintended effects of antidepressants in an ageing population. December 16, 2015.
- Raymond Noordam. Pharmaco-epidemiological studies on antidepressant use in older adults. July 3, 2015
Non-scientific publications related to the ACE
Principal coordinator(s)
Leading investigator(s)
- K.M. Allegaert
- A.H.J. Danser
- M. Dijk
- R. Flint
- S.L.W. Koolen
- H. Kuy
- M.P.J.K. Lolkema
- J.W. Mouton
- A.J.M. Roks
- F Rosse
- L.M.E. Staals
- S.M.J.M. Straus
- B.H.C. Stricker
- M.C.J.M. Sturkenboom
- V. Valkenburg
- P.M.L.A. van den Bemt
- T. van Gelder
- A. Van Haren-Maassen van den Brink
- R.H.N. van Schaik
- K.M.C. Verhamme
- J. Versmissen
- B. Winter
- C.M. Zwaan