A5016360672- Diabetes Treatment and Management
- Estrogen and related hormone effects
- Inflammatory mediators and NSAID effects
- Bioactive Compounds and Antitumor Agents
- Receptor Mechanisms and Signaling
- Diabetes Management and Research
- Pharmacology and Obesity Treatment
- Atrial Fibrillation Management and Outcomes
- Statistical Methods in Clinical Trials
- Hormonal and reproductive studies
- Diet and metabolism studies
- Sexual Differentiation and Disorders
- Bryophyte Studies and Records
- Metal-Catalyzed Oxygenation Mechanisms
- Lung Cancer Treatments and Mutations
- Lung Cancer Research Studies
- Metabolism, Diabetes, and Cancer
- Computational Drug Discovery Methods
- Pharmaceutical industry and healthcare
- Pharmacological Effects and Toxicity Studies
- Medication Adherence and Compliance
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Migraine and Headache Studies
- Biosimilars and Bioanalytical Methods
- Metabolomics and Mass Spectrometry Studies
PNO Consultants (Netherlands)
2021-2024
Erasmus MC
2024
Merck & Co., Inc., Rahway, NJ, USA (United States)
2013-2019
MSD (Netherlands)
2012-2015
Meander Medisch Centrum
2011
Vrije Universiteit Amsterdam
1988-2006
Abstract Background and Purpose Cotadutide is a dual GLP‐1 glucagon receptor agonist with balanced agonistic activity at each designed to harness the advantages on promoting liver health, weight loss glycaemic control. We characterised effects of cotadutide glucose, insulin, GLP‐1, GIP, over time in quantitative manner using our glucose dynamics systems model (4GI model), combination clinical data from multiple ascending dose/Phase 2a (MAD/Ph2a) study overweight obese subjects history Type 2...
The progesterone receptor is able to bind a large number and variety of ligands that elicit broad range transcriptional responses ranging from full agonism antagonism numerous mixed profiles inbetween. We describe here two new ligand binding domain x-ray structures bound compounds structurally related but functionally divergent series, which show different modes corresponding their agonistic or antagonistic nature. In addition, we present third dimer an agonist in monomer A antagonist B,...
Abstract Merck & Co., Inc. (Kenilworth, New Jersey) has recently published an integrated strategy for implementation of dried blood spots (DBS) in late‐stage trials population pharmacokinetic (PK) modeling. We applied this another clinical program: ubrogepant (MK‐1602), a novel oral calcitonin gene‐related peptide receptor antagonist acute treatment migraine. At the time implementation, was entering phase 2 development. DBS implemented to acquire PK information proximal migraine event...
In pharmacometric modeling, it is often important to know whether the data sufficiently rich identify parameters of a proposed model. While may be possible assess this based on results model fit, difficult disentangle identifiability issues from other fitting and numerical problems. Furthermore, can value ascertain beforehand. This paper compares four methods for parameter identifiability, namely Differential Algebra Identifiability SYstems (DAISY), sensitivity matrix method (SMM), Aliasing,...
Abstract Obesity has become a major public health concern worldwide. Pharmacological interventions with the glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) have shown promising results in facilitating weight loss and improving metabolic outcomes individuals obesity. Quantifying drug effects of GLP‐1RAs on energy intake (EI) body (BW) using QSP modeling approach can further increase mechanistic understanding these effects, support obesity development. An extensive literature‐based...
Androgen receptor (AR) mutations in androgen insensitivity syndrome (AIS) are associated with a variety of clinical phenotypes. The aim the present study was to compare molecular properties and potential pathogenic nature 8 novel 3 recurrent AR variants broad functional assays. Eleven (p.Cys177Gly, p.Arg609Met, p.Asp691del, p.Leu701Phe, p.Leu723Phe, p.Ser741Tyr, p.Ala766Ser, p.Arg775Leu, p.Phe814Cys, p.Lys913X, p.Ile915Thr) were analyzed for hormone binding, transcriptional activation,...
Ubrogepant (MK‐1602) is a novel, oral, calcitonin gene‐related peptide receptor antagonist in clinical development with positive phase III outcomes for acute treatment of migraine. This paper describes the population exposure‐response (E‐R) modeling and simulations, which were used to inform dose‐selection rationale, based on ~ 800 participants pooled across two IIb randomized dose‐finding trials. The E‐R model placebo ubrogepant effects migraine pain end points (2‐hour relief 2‐hour...
Flora and vegetation of the Dutch, German Danish Wadden Islands were compared with aid similarity computer programs. The District, often described as an exclusively Dutch phytogeographical entity, was found to cover whole area. From a comparison floras neighbouring Dune Haff District more distant Kempen it concluded that forms distinct unity by its relatively large internal cohesion. Within three groups islands could be discerned: western group including Borkum, central northern partly...