Nielka Van Erp and Roger Brüggemann of the division of pharmacy have both received a grant for personalized health care from NWO, in the program of Goed Gebruik Geneesmiddelen of ZonMW.
The grants have been awarded for the proposal REFINE (519.000 euro) and for the proposal AMIGO (246.000 euro).
AMIGO focuses on the behaviour (pharmacokinetics (PK)) of antimicrobial agents in morbidly obese patients. Early, adequate and optimal treatment (the proper drug in the correct dose) is of the greatest essence to promote survival of our patients with bacterial infections. Knowledge on the pharmacokinetics of antibacterial drugs in morbidly obese patients is very limited. As the prevalence of obesity is dramatically increasing this problem is even more pronounced. Obese patients are subject to a variety of (patho)physiological changes compared to non-obese patients which results in alteration of the pharmacokinetic profile of these antimicrobials. The consequence in lack of PK knowledge is that optimal dosing may be compromised.
The goal of our study is to develop dosig guidelines for vancomycine, gentamicin and tobramycin in morbidly obese patients by characterising the pharmacokinetics in this population. These concentrations are then put into perspective with regards to the predefined targetconcentrations for optimal treatment.
The AMIGO is conducted together with the department of pharmacy of the St. Antonius hospital in Nieuwegein in close collaboration with the department of surgery and anesthesiology of the St Antonius hospitalas well as the department of medical microbiology (Radboudumc) and the department of pharmacy of the UMCG.
In the REFINE-project we would like to determine whether early easily assessable and potentially more predictive biomarkers can be used to discriminate between patients who will develop 1. objective durable response; 2. suboptimal short response or who are 3. de novo resistant to the novel anti-androgen therapy. Additionally we would like to determine the relation between anti-androgen (abiraterone and enzalutamide) plasma concentrations and the decrease in these promising predictive biomarkers.
Finally, we would like to determine what the effect of patient characteristics (e.g. age, ethnics, weight) is on the exposure to enzalutamide and abiraterone in the large diverse cohort of patients who are currently treated with these drugs.
The pharmaco-dynamic biomarkers of interest in this study are: circulating tumor mRNAs: PSA mRNA, PCA3 mRNA, TMPRSS2:ERP gene fusion and ARv7 (splice variant 7) mRNA and ARwt (full length) mRNA together with a panel of promising microRNAs (in plasma): miR-21, miR-141, miR-200a as well as three microRNAs discovered in our own institute miRrumc95, miRrumc87 and miRrumc4417.
The pharmacokinetic biomarkers of interest in this study are: abiraterone, enzalutamide and N-desmethyl enzalutamide concentrations in plasma. By discriminating between the patients that are initially resistant, suboptimally dosed or adequately treated shortly after treatment initiation, along with the identification of patients characteristics that influence drug exposure this project aims to bring timely treatment optimization for the individual patient within reach.
The REFINE project is the product of an established collaboration between the department of Urology, Medical Oncology, Health Economics and Pharmacy of the RadboudUMC as well as the Jeroen Bosch Hospital (medical oncology), Canisius Wilhelmina Hospital (Urology), Isala Clinic (medical oncology, VUmc (medical oncology) and NKI-AvL (clinical Pharmacology).
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