Elke Krekels
Guest
- Name
- Dr. E.H.J. Krekels
- Telephone
- 071 5276211
- e.h.j.krekels@lacdr.leidenuniv.nl
- ORCID iD
- 0000-0001-6006-1567

Elke Krekels is assistant professor at the Division of Systems Biomedicine and Pharmacology.
More information about Elke Krekels
PhD Candidates
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Former PhD candidates
Dr. Elke H.J. Krekels developed a keen interest in pharmacometrics (i.e. model-based pharmacological research), during her BSc and MSc studies Biopharmaceutical Sciences at Leiden University. For this she performed three internships focusing on preclinical pharmacological research questions; two at the Division of Pharmacology of the Leiden Academic Centre for Drug Research (LACDR) and one at the pharmaceutical company AstraZeneca in Södertälje, Sweden.
Her PhD research, which was a collaboration between the Division of Pharmacology of the LACDR and the Department of Pediatric Surgery and Intensive Care from the Erasmus MC/Sophia Children’s Hospital in Rotterdam, aimed at developing and validating novel, model-based approaches to establish drug dosing recommendations for children. For this she developed population pharmacokinetic models that allowed her to optimize the regimen of specific drugs (e.g. morphine in post-operative newborns and infants) by correcting for differences in drug exposure between patients of different ages. Additionally, she developed novel concepts to derive generalizable dose recommendations for drugs that share elimination routes. For her work she received the PhD thesis award as well as the Best Publication Award from Dutch Society for Clinical Pharmacology & Biopharmacy (NVKF&B) in 2012.
In 2012, Dr. Krekels started a two-year postdoctoral research position at the Pharmacometrics Research Group at Uppsala University, Sweden. Here she expanded her pharmacometric skills by applying item response theory to longitudinal data of disease severity measures for schizophrenia that are based on a multi-item questionnaire-based clinical scale (i.e. PANSS). She was the first to apply item response theory for a clinical scale that consists of multiple sub-scales. In addition, Dr. Krekels performed a population pharmacokinetic analysis of data from a phase 3 clinical trial including more than 10,000 patients for the drug edoxaban that was in the clinical drug development phase at that time.
As an assistant professor at the Division of Systems Biomedicine and Pharmacology of the LACDR, Dr. Krekels currently continues to work on developing new strategies for optimizing paediatric drug dosing recommendations taking both pharmacokinetics as well as pharmacodynamics into account. In 2015 she also joined a research collaboration between colleagues from the LACDR and from the Institute Biology Leiden (IBL) which initiated the first translational pharmacological research line in zebrafish larvae.
In 2018 she received a personal Off Road research grant (ZonMw) that allowed her to develop a preclinical experimental model to study neonatal sepsis in zebrafish larvae. The ultimate aim of this research line is to obtain relatively large amounts of data from this experimental model and use this in combination with existing but inherently sparse clinical data, to develop a Quantitative Systems Pharmacology (QSP) model for neonatal sepsis. This model will generate an integrated understanding of this disease mechanism for neonatal sepsis, which is imperative for the identification of prognostic biomarkers and new treatment targets for this disease.
For the bachelor's and master's programmes Biopharmaceutical Sciences Dr. Krekels teaches on pharmacology and pharmacometrics as well as on scientific research and drug development in general. As an active member of the teaching team of these bachelor's and master's programmes, she contributes to the design and restructuring of the curriculum and implementation of teaching innovations. She is particularly motivated to promote inclusion of computational-based research in the programme curricula.
Guest
- Science
- Leiden Academic Centre for Drug Research
- LACDR/Pharmacology
- Di X., Martinez-Tellez B., Krekels E.H.J., Jurado-Fasoli L., Osuna-Prieto F.J., Ortiz-Alvarez L., Hankemeier T., Rensen P.C.N., Ruiz J.R. & Kohler I. (2024), Higher plasma levels of endocannabinoids and analogues correlate with a worse cardiometabolic profile in young adults, The Journal of Clinical Endocrinology and Metabolism 109(5): 1351-1360.
- Zhang T., Calvier E.A.M., Krekels E.H.J. & Knibbe C.A.J. (2024), Impact of obesity on hepatic drug clearance: what are the influential variables?, AAPS Journal 26(3): 59.
- Wu Y., Allegaert K., Flint R.B., Goulooze S.C., Valitalo P.A.J., Hoog M. de, Mulla H., Sherwin C.M.T., Simons S.H. P., Krekels E.H.J., Knibbe C.A.J. & Völler S. (2024), When will the glomerular filtration rate in former preterm neonates catch up with their term peers?, Pharmaceutical Research 41(4): 637-649.
- Valkengoed D.W. van, Krekels E.H.J. & Knibbe C.A.J. (2024), All you need to know about allometric scaling: an integrative review on the theoretical basis, empirical evidence, and application in human pharmacology, Clinical Pharmacokinetics 64: 173-192.
- Jong L.M. de, Kreeke A.M. van de, Ahmadi M., Swen J.J., Knibbe C.A.J., Hasselt J.G.C. van, Manson M.L. & Krekels E.H.J. (2024), Changes in plasma clearance of CYP450 probe drugs may not be specific for altered in vivo enzyme activity under (patho)physiological conditions : how to interpret findings of probe cocktail studies, Clinical Pharmacokinetics 63(11): 1585-1595.
- Chen L., Krekels E.H.J., Heijnen A.R., Knibbe C.A.J. & Brüggemann R.J. (2023), An integrated population pharmacokinetic analysis for posaconazole oral suspension, delayed-release tablet, and intravenous infusion in healthy volunteers, Drugs 83: 75-86.
- Zhang T., Smit C., Sherwin C.M.T., Knibbe C.A.J. & Krekels E.H.J. (2023), Vancomycin clearance in obese adults is not predictive of clearance in obese adolescents, Clinical Pharmacokinetics 62(5): 749-759.
- Liu F., Aulin L.B.S. & Manson M.L. Krekels E.H.J. Hasselt J.G.C. van (2023), Unraveling the effects of acute inflammation on pharmacokinetics: a model-based analysis focusing on renal glomerular filtration rate and cytochrome P450 3A4-mediated metabolism, European Journal of Drug Metabolism and Pharmacokinetics 48: 623–631.
- Wu Y., Völler S., Krekels E.H.J., Roofthooft D.W.E., Simons S.H.P., Tibboel D., Flint R.B. & Knibbe C.A.J. (2023), Maturation of paracetamol elimination routes in preterm neonates born below 32 weeks of gestation, Pharmaceutical Research 40(9): 2155-2166.
- Jurado-Fasoli L., Di X., Sanchez-Delgado G., Yang W., Osuna-Prieto F.J., Ortiz-Alvarez L., Krekels E., Harms A.C., Hankemeier T., Schonke C., Aguilera C.M., Llamas-Elvira J.M., Kohler I., Rensen P.C.N., Ruiz J.R. & Martinez-Tellez B. (2022), Acute and long-term exercise differently modulate plasma levels of oxylipins, endocannabinoids, and their analogues in young sedentary adults: A sub-study and secondary analyses from the ACTIBATE randomized controlled-trial, EBioMedicine 85: 104313.
- Jurado-Fasoli L., Di X.Y., Kohler I., Osuna-Prieto F.J., Hankemeier T., Krekels E.H.J., Harms A.C., Yang W., Garcia-Lario J.V., Fernandez-Veledo S., Ruiz J.R., Rensen P.C.N. & Martinez-Tellez B. (2022), Omega-6 and omega-3 oxylipins as potential markers of cardiometabolic risk in young adults, Obesity 30(1): 50-61.
- Liu F., Aulin L.B.S., Guo T., Krekels E.H.J., Moerland M., Graaf P.H. van der & Hasselt J.G.C. van (2022), Modelling inflammatory biomarker dynamics in a human lipopolysaccharide (LPS) challenge study using delay differential equations, British Journal of Clinical Pharmacology 88(12): 5420-5427.
- Rongen A. van, Krekels E.H.J., Calvier E.A.M., Wildt S.N. de, Vermeulen A. & Knibbe C.A.J. (2022), An update on the use of allometric and other scaling methods to scale drug clearance in children: towards decision tables, Expert Opinion on Drug Metabolism & Toxicology 18(2): 99-113.
- Rhee K.P. van, Smit C., Wasmann R.E., Linden P.D. van der, Wiezer R., Dongen E.P. A. van, Krekels E.H.J., Brüggemann R.J.M. & Knibbe C.A.J. (2022), Ciprofloxacin pharmacokinetics after oral and intravenous administration in (morbidly) obese and non-obese individuals: a prospective clinical study, Clinical Pharmacokinetics 61(8): 1167-1175.
- Zhang T., Krekels E.H.J., Smit C. & Knibbe C.A.J. (2022), Drug pharmacokinetics in the obese population: challenging common assumptions on predictors of obesity-related parameter changes, Expert Opinion on Drug Metabolism & Toxicology 18(10): 657-674.
- Wu Y.J., Allegaert K., Flint R.B., Simons S.H.P., Krekels E.H.J., Knibbe C.A.J. & Völler S. (2022), Prediction of glomerular filtration rate maturation across preterm and term neonates and young infants using inulin as marker, AAPS Journal 24(2): 38.
- Engbers A.G.J., Völler S., Flint R.B., Goulooze S.C., Klerk J. de, Krekels E.H.J., Dijk M. van, Willemsen S.P., Reiss I.K.M., Knibbe C.A.J. & Simons S.H.P. (2022), The effect of ibuprofen exposure and patient characteristics on the closure of the patent Ductus Arteriosus in preterm infants, Clinical Pharmacology & Therapeutics 112(2): 307-315.
- Chen L., Rhee K.P. van, Wasmann R.E., Krekels E.H.J., Wiezer M.J., Dongen E.P.A., Verweij P.E., Linden P.D., Bruggemann R.J. & Knibbe C.A.J. (2022), Total bodyweight and sex both drive pharmacokinetic variability of fluconazole in obese adults, Journal of Antimicrobial Chemotherapy 77(8): 2217-2226.
- Jurado-Fasoli L., Yang W., Kohler I., Dote-Montero M., Osuna-Prieto F.J., Di X., Hankemeier T., Krekels E.H.J., Harms A.C., Castillo M.J., Amaro-Gahete F.J. & Martinez-Tellez B. (2022), Effect of different exercise training modalities on fasting levels of oxylipins and endocannabinoids in middle-aged sedentary adults: a randomized controlled trial, International Journal of Sport Nutrition and Exercise Metabolism 32(4): 275-284.
- He B.S., Di X., Gulded F., Harder A.V.E., Maagdenberg A.M.J.M. van den, Terwindt G.M., Krekels E.H.J., Kohler I., Harms A.C., Ramautar R. & Hankemeier T. (2022), Quantification of endocannabinoids in human cerebrospinal fluid using a novel micro-flow liquid chromatography-mass spectrometry method, Analytica Chimica Acta 1210: 339888.
- Groen B.D. van, Krekels E.H.J., Mooij M.G. Duijn E. van Vaes W.H.J., Windhorst A.D.,Rosmalen J. Hartman S.J.F., Hendrikse N.H., Koch B.C.P., Allegaert K., Tibboel D., Knibbe C.A.J. & Wildt S.N. (2021), The oral bioavailability and metabolism of midazolam in stable critically ill children: A pharmacokinetic microtracing study, Clinical Pharmacology & Therapeutics 109(1): 140-149.
- Goulooze S.C., Krekels E.H.J., Saleh M.A.A.E.W., Ahlers S.J., Valitalo P.A.J., Dongen E.P. van, Schaik R.H. van, Hankemeier T., Tibboel D. & Knibbe C.A.J. (2021), Predicting unacceptable pain in cardiac surgery patients receiving morphine maintenance and rescue doses: a model-based pharmacokinetic-pharmacodynamic analysis, Anesthesia and Analgesia 132(3): 726-734.
- Cristea S., Krekels E.H.J., Allegaert K., Paepe P. de, Jaeger A. de, Cock P. de & Knibbe C.A.J. (2021), Estimation of ontogeny functions for renal transporters using a combined population pharmacokinetic and physiology-based pharmacokinetic approach: application to OAT1,3, AAPS Journal 23(3): 65.
- Hoogd S. de, Goulooze S.C., Valkenburg A.J., Krekels E.H.J., Dijk M. van, Tibboel D. & Knibbe C.A.J. (2021), Postoperative breakthrough pain in paediatric cardiac surgery not reduced by increased morphine concentrations, Pediatric Research 90: 1201-1206.
- Goulooze S.C., Ista E., Dijk M. van, Tibboel D., Krekels E.H.J. & Knibbe C.A.J. (2021), Towards evidence-based weaning: a mechanism-based pharmacometric model to characterize iatrogenic withdrawal syndrome in critically ill children, AAPS Journal 23(4): 71.
- Keij F.M., Koch B.E.V., Lozano Vigario F., Simons S.H.P., Hasselt J.G.C. van, Knibbe C.A.J., Spaink H.P., Reiss I.K.M. & Krekels E.H.J. (2021), Zebrafish larvae as experimental model to expedite the search for new biomarkers and treatments for neonatal sepsis, Journal of Clinical and Translational Science 5(1): e140.
- Upadhyay P., Vet N.J., Goulooze S.C., Krekels E.H.J., Wildt S.N. de & Knibbe C.A.J. (2021), Midazolam infusion and disease severity affect the level of sedation in children: a parametric time-to-event analysis, Pharmaceutical Research 38: 1711-1720.
- Hartman S., Upadhyay P., Hagedoorn N., Krekels E.H.J., Mathot R., Moll H., Flier M. van der, Schreuder M., Bruggemann R., Knibbe C.A.J. & Wildt S. de (2021), Population pharmacokinetics of ceftriaxone in critically ill children, Critical Care Medicine 49(1): 425.
- Goulooze S.C., Kluis T. de, Dijk M. van, Ceelie I., Wildt S.N. de, Tibboel D., Krekels E.H.J. & Knibbe C.A.J. (2021), Quantifying the pharmacodynamics of morphine in the treatment of postoperative pain in preverbal children, The Journal of Clinical Pharmacology 62(1): 99-109.
- Jurado-Fasoli L., Di X.Y., Kohler I., Osuna-Prieto F.J., Hankemeier T., Krekels E.H.J., Harms A.C., Yang W., Garcia-Lario J.V., Fernendez-Veledo S., Ruiz J.R., Rensen P.C.N. & Martinez-Tellez B. (2021), Omega-6 and omega-3 oxylipins as potential markers of cardiometabolic risk in young adults, Obesity 30(1): 50-61.
- Goulooze S.C., Zwep L.B., Vogt J.E., Krekels E.H.J., Hankemeier T., Anker J.N. van den & Knibbe C.A.J. (2020), Beyond the randomized clinical trial: innovative data science to close the pediatric evidence gap, Clinical Pharmacology & Therapeutics 107(4): 786-795.
- Wijk R.C. van, Sar A.M. van der, Krekels E.H.J., Verboom T., Spaink H.P., Simonsson U.S.H. & Graaf P.H. van der (2020), Quantification of natural growth of two strains of Mycobacterium marinum for translational anti‐tuberculosis drug development, Clinical and Translational Science 13(6): 1060-1064.
- Valkenburg A.J., Goulooze S.C., Ng C.Y., Breatnach C.V., Tibboel D., Dijk M. van, Knibbe C.A.J. & Krekels E.H.J. (2020), Exploring the relationship between morphine concentration and oversedation in children after cardiac surgery, The Journal of Clinical Pharmacology 60(9): 1231-1236.
- Michalickova D., Pokorna P., Tibboel D., Slanar O. Knibbe C.A.J. & Krekels E.H.J. (2020), Rapid increase in clearance of phenobarbital in neonates on extracorporeal membrane oxygenation: A pilot retrospective population pharmacokinetic analysis, Pediatric Critical Care Medicine 21(9): E707-E715.
- Cristea S., Krekels E.H.J., Rostami-Hodjegan A., Allegaert K. & Knibbe C.A.J. (2020), The influence of drug properties and ontogeny of transporters on pediatric renal clearance through glomerular filtration and active secretion: a simulation-based study, AAPS Journal 22(4): 87.
- Cristea S., Krekels E.H.J., Allegaert K. & Knibbe C.A.J. (2020), The predictive value of glomerular filtration rate-based scaling of pediatric clearance and doses for drugs eliminated by glomerular filtration with varying protein-binding properties, Clinical Pharmacokinetics 59: 1291-1301.
- Wijk R.C. van, Hu W.B., Dijkema S.M., Berg D. van den, Liu J., Bahi R., Verbeek F.J., Simonsson U.S.H., Spaink H.P., Graaf P.H. van der & Krekels E.H.J. (2020), Anti-tuberculosis effect of isoniazid scales accurately from zebrafish to humans, British Journal of Pharmacology 177(24): 5518-5533.
- Michalickova D., Jansa P., Bursova M., Hlozek T., Cabala R., Hartinger J.M., Ambroz D., Aschermann M., Lindner J., Linhart A., Slanar O. & Krekels E.H.J. (2020), Population pharmacokinetics of riociguat and its metabolite in patients with chronic thromboembolic pulmonary hypertension from routine clinical practice, Pulmonary Circulation 10(1): 1-11.
- Chen L., Krekels E.H.J., Verweij P.E., Buil J.B., Knibbe C.A.J. & Brüggemann R.J.M. (2020), Pharmacokinetics and pharmacodynamics of posaconazole, Drugs 80(7): 671-695.
- Krekels E.H.J., Calvier E.A.M., Graaf P.H. van der & Knibbe C.A.J. (2019), Children Are Not Small Adults, but Can We Treat Them As Such?, CPT: Pharmacometrics and Systems Pharmacology 8(1): 34-38.
- Wijk R.C. van, Krekels E.H.J., Kantae V., Harms A.C., Hankemeier T., Graaf P.H. van der & Spaink H.P. (2019), Impact of post-hatching maturation on the pharmacokinetics of paracetamol in zebrafish larvae, Scientific Reports 9: 2149.
- Wijk R.C. van, Krekels E.H.J., Kantae V., Ordas A., Kreling T., Harms A.C., Hankemeier T., Spaink H.P. & Graaf P.H. van der (2019), Mechanistic and quantitative understanding of pharmacokinetics in zebrafish larvae through nanoscale blood sampling and metabolite modelling of paracetamol, Journal of Pharmacology and Experimental Therapeutics 371(1): 15-24.
- Kleiber N., Calvier E., Mooij M.G., Krekels E.H.J., Vaes W.H.J., Tibboel D., Knibbe C.A.J. & Wildt S.N. de (2019), Enteral acetaminophen bioavailability in pediatric intensive care patients determined with an oral microtracer and pharmacokinetic modeling to pptimize dosing, Critical Care Medicine 47(12): e975-e983.
- Brussee J.M., Krekels E.H.J., Calvier E.A.M., Palic S., Rostami-Hodjegan A., Danhof M., Barrett J.S., Wildt S.N. de & Knibbe C.A.J. (2019), A Pediatric Covariate Function for CYP3A-Mediated Midazolam Clearance Can Scale Clearance of Selected CYP3A Substrates in Children, AAPS Journal 21(5): 81.
- Groen B.D. van, Vaes W.H., Park B.K., Krekels E.H.J., Duijn E. van, Körgvee L.-T., Maruszak W., Grynkiewicz G., Garner R.C., Knibbe C.A.J., Tibboel D., Wildt S.N. de & Turner M.A. (2019), Dose‐linearity of the pharmacokinetics of an intravenous [14C]midazolam microdose in children, British Journal of Clinical Pharmacology 85(10): 2332-2340.
- Cristea S., Allegaert K., Falcao A.C., Falcao F., Silva R., Smits A., Knibbe C.A.J. & Krekels E.H.J. (2019), Larger Dose Reductions of Vancomycin Required in Neonates with Patent Ductus Arteriosus Receiving Indomethacin versus Ibuprofen, Antimicrobial Agents and Chemotherapy 63(8): e00853.
- Calvier E.A.M., Krekels E.H.J., Johnson T.N., Rostami-Hodjegan A., Tibboel D. & Knibbe C.A.J. (2019), Scaling Drug Clearance from Adults to the Young Children for Drugs Undergoing Hepatic Metabolism: A Simulation Study to Search for the Simplest Scaling Method, AAPS Journal 21(3): 38.
- Mian R., Valkenburg A.J., Allegaert K., Koch B.C.P., Breatnach C.V., Knibbe C.A.J., Tibboel D. & Krekels E.H.J. (2019), Population Pharmacokinetic Modeling of Acetaminophen and Metabolites in Children After Cardiac Surgery With Cardiopulmonary Bypass, The Journal of Clinical Pharmacology 59(6): 847-855.
- Russo F.M., Mian P., Krekels E.H., Calsteren K. van, Tibboel D., Deprest J. & Allegaert K. (2019), Pregnancy affects the pharmacokinetics of sildenafil and its metabolite in the rabbit, Xenobiotica 49(1): 98-105.
- Goulooze S.C., Ista E., Dijk M. van, Hankemeier T., Tibboel D., Knibbe C.A.J. & Krekels E.H.J. (2019), Supervised Multidimensional Item Response Theory Modeling of Pediatric Iatrogenic Withdrawal Symptoms, CPT: Pharmacometrics and Systems Pharmacology 8(12): 904-912.
- Krekels E.H.J. & Knibbe C.A.J. (2019), Pharmacokinetics and pharmacodynamics of drugs in obese pediatric patients: how to map uncharted clinical territories. In: Kiess W., Schwab M. & Anker J. van den (Eds.), Pediatric Pharmacotherapy . Handbook of Experimental Pharmacology no. 261. Cham: Springer. 231-255.
- Goulooze S.C., Völler S., Valitalo P.A.J., Calvier E.A.M., Aarons L., Krekels E.H.J. & Knibbe C.A.J. (2019), The Influence of Normalization Weight in Population Pharmacokinetic Covariate Models, Clinical Pharmacokinetics 58(1): 131-138.
- Goulooze S.C., Krekels E.H.J., Hankemeier T. & Knibbe C.A.J. (2019), Covariates in Pharmacometric Repeated Time-to-Event Models: Old and New (Pre)Selection Tools, AAPS Journal 21: 11.
- Brussee J.M., Vet N.J., Krekels E.H.J., Valkenburg A.J., Jacqz-Aigrain E., Gerven J.M.A. van, Swart E.L., Anker J.N. van den, Tibboel D., Hoog M. de, Wildt S.N. de & Knibbe C.A.J. (2018), Predicting CYP3A-mediated midazolam metabolism in critically ill neonates, infants, children and adults with inflammation and organ failure, British Journal of Clinical Pharmacology 84(2): 358-368.
- Goulooze S.C., Välitalo P.A.J., Knibbe C.A.J. & Krekels E.H.J. (2018), Kernel-Based Visual Hazard Comparison (kbVHC): a Simulation-Free Diagnostic for Parametric Repeated Time-to-Event Models, AAPS Journal 20(1): 5.
- Calvier E.A.M., Krekels E.H.J., Yu H., Välitalo P.A.J., Johnson T.N., Rostami-Hodjegan A., Tibboel D., Graaf P.H. van der, Danhof M. & Knibbe C.A.J. (2018), Drugs Being Eliminated via the Same Pathway Will Not Always Require Similar Pediatric Dose Adjustments, CPT: Pharmacometrics and Systems Pharmacology 7(3): 175-185.
- Schulthess P., Wijk R.C. van, Krekels E.H.J., Yates J.W.T., Spaink H.P. & Graaf P.H. van der (2018), Outside-in systems pharmacology combines innovative computational methods with high-throughput whole vertebrate studies, CPT: Pharmacometrics and Systems Pharmacology 7(5): 285-287.
- Calvier E.A.M., Thu T.N., Johnson T.N., Rostami-Hodjegan A., Tibboel D., Krekels E.H.J. & Knibbe C.A.J. (2018), Can Population Modelling Principles be Used to Identify Key PBPK Parameters for Paediatric Clearance Predictions? An Innovative Application of Optimal Design Theory, Pharmaceutical Research 35(11): 209.
- Brussee J.M., Yu H., Krekels E.H.J., Palic S., Brill M.J.E., Barrett J.S., Rostami-Hodjegan A., Wildt S.N. de & Knibbe C.A.J. (2018), Characterization of Intestinal and Hepatic CYP3A-Mediated Metabolism of Midazolam in Children Using a Physiological Population Pharmacokinetic Modelling Approach, Pharmaceutical Research 35: 182.
- Brussee J.M., Yu H., Krekels E.H.J., Roos B. de, Brill M.J.E., Anker J.N. van den, Rostami-Hodjegan A., Wildt S.N. de & Knibbe C.A.J. (2018), First-Pass CYP3A-Mediated Metabolism of Midazolam in the Gut Wall and Liver in Preterm Neonates, CPT: Pharmacometrics and Systems Pharmacology 7(6): 374-383.
- Zeilmaker G.A., Pokorna P., Mian P., Wildschut E.D., Knibbe C.A.J., Krekels E.H.J., Allegaert K. & Tibboel D. (2018), Pharmacokinetic considerations for pediatric patients receiving analgesia in the intensive care unit; targeting postoperative, ECMO and hypothermia patients, Expert Opinion on Drug Metabolism & Toxicology 14(4): 417-428.
- Kantae V., Krekels E.H.J., Esdonk M.J. van, Lindenburg P.W., Harms A.C., Knibbe C.A.J., Graaf P.H. van der & Hankemeier T. (2017), Integration of pharmacometabolomics with pharmacokinetics and pharmacodynamics: towards personalized drug therapy, Metabolomics 13(1): 9.
- Calvier E.A.M., Krekels E.H.J., Välitalo P.A.J., Rostami-Hodjegan A., Tibboel D., Danhof M. & Knibbe C.A.J. (2017), Allometric Scaling of Clearance in Paediatric Patients: When Does the Magic of 0.75 Fade?, Clinical Pharmacokinetics 56(3): 273-285.
- Wijk R.C. van, Krekels E.H.J., Hankemeier T., Spaink H.P. & Graaf P.H. van der (2017), Systems pharmacology of hepatic metabolism in zebrafish larvae, Drug Discovery Today: Disease Models 22: 27-34.
- Kantae V., Krekels E.H.J., Esdonk M.J. van, Lindenburg P.W., Harms A.C., Knibbe C.A.J., Graaf P.H. van der & Hankemeier T. (2017), Integration of pharmacometabolomics with pharmacokinetics and pharmacodynamics: towards personalized drug therapy: an addition to the topical collection "Recent Advances in Pharmacometabolomics: Enabling Tools for Precision Medicine", Metabolomics 13(5): 58.
- Goulooze S.C., Krekels E.H.J., Dijk M. van, Tibboel D., Graaf P.H. van der, Hankemeier T., Knibbe C.A.J. & Hasselt J.G.C. van (2017), Towards personalized treatment of pain using a quantitative systems pharmacology approach, European Journal of Pharmaceutical Sciences 109: S32-S38.
- Guo Y., Wijk R.C. van, Krekels E.H.J., Spaink H.P., Graaf P.H. van der & Verbeek F.J. (2017), Multi-modal 3D reconstruction and measurements of zebrafish larvae and its organs using axial-view microscopy, 2017 IEEE International conference on image processing (ICIP). IEEE International Conference on Image Processing 2017 17 September 2017 - 20 September 2017: IEEE Xplore. 2194-2198.
- Krekels E.H.J., Hasselt J.G.C. van, Anker J.N. van den, Allegaert K., Tibboel D. & Knibbe C.A.J. (2017), Evidence-based drug treatment for special patient populations through model-based approaches, European Journal of Pharmaceutical Sciences 109(Supplement): S22-S26.
- Valitalo P.A.J., Krekels E.H.J., Dijk M. van, Simons S.H.P., Tibboel D. & Knibbe C.A.J. (2017), Morphine Pharmacodynamics in Mechanically Ventilated Preterm Neonates Undergoing Endotracheal Suctioning, CPT: Pharmacometrics and Systems Pharmacology 6(4): 239-248.
- Kantae V., Krekels E.H.J., Ordas A.K., Gonzalez O., Wijk R.C. van, Harms A.C., Racz P.I., Graaf P.H. van der, Spaink H.P. & Hankemeier T. (2016), Pharmacokinetic modeling of paracetamol uptake and clearance in zebrafish larvae: expanding the allometric scale in vertebrates with five orders of magnitude, Zebrafish 13(6): 504-510.
- Valkenburg A.J, Calvier E.A.M., Dijk M. van, Krekels E.H.J., O'Hare B.P., Casey W.F., Mathôt R.A., Knibbe C.A.J, Tibboel D. & Breatnach C.V. (2016), Pharmacodynamics and Pharmacokinetics of morphine after cardiac surgery in children with and without Down Syndrome, Pediatric Critical Care Medicine 17(10): 930-938.
- Krekels E.H., Niebecker R., Karlsson M.O., Miller R., Shimizu T., Karlsson K.E., Ruff C.T., Simonsson U.S. & Jönsson S. (2016), Population Pharmacokinetics of Edoxaban in Patients with Non-Valvular Atrial Fibrillation in the ENGAGE AF-TIMI 48 Study, a Phase III Clinical Trial, Clinical Pharmacokinetics 55(9): 1079-1090.
- Brussee J.M., Calvier E.A., Krekels E.H.J., Välitalo P.A.J., Tibboel D., Allegaert K. & Knibbe C.A. (2016), Children in clinical trials: towards evidence-based pediatric pharmacotherapy using pharmacokinetic-pharmacodynamic modeling, Expert Review of Clinical Pharmacology 9(9): 1235-1244.
- Välitalo P.A., Dijk M. van, Krekels E.H.J., Gibbins S., Simons S.H., Tibboel D. & Knibbe C.A.J. (2016), Pain and distress caused by endotracheal suctioning in neonates is better quantified by behavioural than physiological items: a comparison based on item response theory modelling, Pain 157(8): 1611-1617.
- Novakovic A.M., Krekels E.H., Munafo A., Ueckert S. & Karlsson M.O. (2016), Application of Item Response Theory to Modeling of Expanded Disability Status Scale in Multiple Sclerosis, AAPS Journal 19: 172.
- Niebecker R., Jönsson S., Karlsson M.O., Miller R., Nyberg J., Krekels E.H.J. & Simonsson U.S. (2015), Population pharmacokinetics of edoxaban in patients with symptomatic deep-vein thrombosis and/or pulmonary embolism-the Hokusai-VTE phase 3 study, British Journal of Clinical Pharmacology 80(6): 1374-1387.
- Krekels E.H.J., Tibboel D. & Knibbe C.A.J. (2015), Pediatric pharmacology: current efforts and future goals to improve clinical practice, Expert Opinion on Drug Metabolism & Toxicology 11(11): 1679-1682.
- Krekels E.H.J., Ham S. van, Allegaert K., Hoon J. de, Tibboel D., Danhof M. & Knibbe C.A.J. (2015), Developmental changes rather than repeated administration drive paracetamol glucuronidation in neonates and infants, European Journal of Clinical Pharmacology 71(9): 1075-82.
- Spaink H., Racz P., Ordas A., Veneman W., Vijver M., Wildwater M., Pieters R., Zope H.R., Kros A., Kantae V., Krekels E., Graaf P.H. van der & Hankemeier T. (2015), Automated zebrafish toxicology screening: effect assessment and uptake studies, Toxicology Letters 238(2): S54-S54.
- Krekels E.H.J., Knibbe C.A.J., Pokorna P. & Tibboel D. (2015), How to Translate Pharmacokinetic Data into Dosing Recommendations. In: Mimouni F.B. & Anker J.N. van den (Eds.), Neonatal Pharmacology and Nutrition Update no. 18. Basel: Karger. 13-27.
- Krekels E.H.J., Tibboel D., Wildt S.N. de, Ceelie I., Dahan A., Dijk M. van, Danhof M. & Knibbe C.A.J. (2014), Evidence-based morphine dosing for postoperative neonates and infants, Clinical Pharmacokinetics 53(6): 553-563.
- Wang C., Sadhavisvam S., Krekels E.H.J., Dahan A., Tibboel D., Danhof M., Vinks A.A. & Knibbe C.A.J. (2013), Developmental changes in morphine clearance across the entire paediatric age range are best described by a bodyweight-dependent exponent model, Clinical Drug Investigation 33(7): 523-534.
- Krekels E.H.J., Johnson T.N., Hoedt S.M. den, Rostami-Hodjegan A., Danhof M., Tibboel D. & Knibbe C.A.J. (2012), From Pediatric Covariate Model to Semiphysiological Function for Maturation: Part II-Sensitivity to Physiological and Physicochemical Properties, CPT: Pharmacometrics and Systems Pharmacology 2012(1): e10.
- Krekels E.H.J., Neely M., Panoilia E., Tibboel D., Capparelli E., Danhof M., Mirochnick M. & Knibbe C.A.J. (2012), From pediatric covariate model to semiphysiological function for maturation: part I-extrapolation of a covariate model from morphine to Zidovudine, CPT: Pharmacometrics and Systems Pharmacology 2012(1): e9.
- Wang C., Peeters M.Y., Allegaert K., Blussé van Oud-Alblas H.J., Krekels E.H.J., Tibboel D., Danhof M. & Knibbe C.A.J. (2012), A bodyweight-dependent allometric exponent for scaling clearance across the human life-span, 29(6): 1570-1581.
- Krekels E.H.J. (10 October 2012), Size does matter : drug glucuronidation in children (Dissertatie, Faculty of Science, Leiden University). Supervisor(s): Knibbe C.A.J. & Tibboel D.
- Krekels E.H.J., Danhof M., Tibboel D. & Knibbe C.A.J. (2012), Ontogeny of hepatic glucuronidation; methods and results, Current Drug Metabolism 13(6): 728-743.
- Sadhasivam S., Krekels E.H.J., Chidambaran V., Esslinger H.R., Ngamprasertwong P., Zhang K., Fukuda T. & Vinks A.A. (2012), Morphine clearance in children: does race or genetics matter?, Journal of Opioid Management 8(4): 217-226.
- Krekels E.H.J., Tibboel D. & Knibbe C.A.J. (2012), Prediction of morphine clearance in the paediatric population : how accurate are the available pharmacokinetic models?, Clinical Pharmacokinetics 51(11): 695-709.
- Knibbe C.A., Krekels E.H. & Danhof M. (2011), Advances in paediatric pharmacokinetics, Expert Opinion on Drug Metabolism & Toxicology 7(1): 1-8.
- Cock R.F.W. de, Piana C., Krekels E.H.J., Danhof M., Allegaert K. & Knibbe C.A.J. (2011), The role of population PK-PD modelling in paediatric clinical research, European Journal of Clinical Pharmacology 67(Suppl 1): 5-16.
- Krekels E.H.J., Angesjö M., Sjögren I., Möller K.A., Berge O.G. & Visser S.A. (2011), Pharmacokinetic-pharmacodynamic modeling of the inhibitory effects of naproxen on the time-courses of inflammatory pain, fever, and the ex vivo synthesis of TXB2 and PGE2 in rats, 28(7): 1561-1576.
- Krekels E.H.J., Hasselt J.G.C. van, Tibboel D., Danhof M. & Knibbe C.A.J. (2011), Systematic evaluation of the descriptive and predictive performance of paediatric morphine population models, Pharmaceutical Research 28(4): 797-811.
- Krekels E.H., DeJongh J., Van Lingen R.A., Van der Marel C.D., Choonara I., Lynn A.M., Danhof M., Tibboel D. & Knibbe C.A. (2011), Predictive performance of a recently developed population pharmacokinetic model for morphine and its metabolites in new datasets of (preterm) neonates, infants and children, Clinical Pharmacokinetics 50(1): 51-63.
- Steeg T.J. van, Krekels E.H.J., Freijer J., Danhof M. & Lange E.C.M. de (2010), Effect of altered AGP plasma binding on heart rate changes by S(-)-propranolol in rats using mechanism-based estimations of in vivo receptor affinity (K(B,vivo)), JOURNAL OF PHARMACEUTICAL SCIENCES 99(5): 2511-2520.
- Steeg T.J. van, Boralli V.B., Krekels E.H.J., Slijkerman P., Freijer J., Danhof M. & Lange E.C.M. de (2009), Influence of plasma protein binding on pharmacodynamics: Estimation of in vivo receptor affinities of beta blockers using a new mechanism-based PK-PD modelling approach, JOURNAL OF PHARMACEUTICAL SCIENCES 98(10): 3816-28.
- Knibbe C.A.J., Krekels E.H.J., Anker J.N. van den, DeJongh J., Santen G.W., Dijk M. van, Simons S.H., Lingen R.A. van, Jacqz-Aigrain E.M., Danhof M. & Tibboel D. (2009), Morphine glucuronidation in preterm neonates, infants and children younger than 3 years, Clinical Pharmacokinetics 48(6): 371-385.
- Krekels E.H.J., Anker J.N. van der, Baiardi P., Cella M., Cheng K.Y., Gibb D.M., Green H., Iolascon A., Jacqz-Aigrain E.M., Knibbe C.A.J., Santen G.W., Schaik R.H. van, Tibboel D. & Della Pasqua O.E. (2007), Pharmacogenetics and paediatric drug development: issues and consequences to labelling and dosing recommendations, Expert Opinion on Pharmacotherapy 8(12): 1787-1799.
- Steeg T.J. van, Krekels E.H.J., Danhof M. & Lange E.C.M. de (2007), Reproducible and time-dependent modification of serum protein binding in Wistar Kyoto rats, Journal of Pharmacological and Toxicological Methods 56(1): 72-78.
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