A5077152954- Pharmacogenetics and Drug Metabolism
- Sleep and Wakefulness Research
- Sleep and related disorders
- Circadian rhythm and melatonin
- Drug Transport and Resistance Mechanisms
- Metabolism and Genetic Disorders
- HIV/AIDS drug development and treatment
- Analytical Chemistry and Chromatography
- Regulation of Appetite and Obesity
- Healthcare Policy and Management
- Primary Care and Health Outcomes
- Folate and B Vitamins Research
- Biosimilars and Bioanalytical Methods
- HIV Research and Treatment
- Blood groups and transfusion
- Mitochondrial Function and Pathology
- Obsessive-Compulsive Spectrum Disorders
- Epilepsy research and treatment
- Chemical Reactions and Isotopes
- Neuroscience and Neuropharmacology Research
- Neurotransmitter Receptor Influence on Behavior
- Plant-based Medicinal Research
- 3D Printing in Biomedical Research
- Receptor Mechanisms and Signaling
- Renal Transplantation Outcomes and Treatments
Idorsia (Switzerland)
2020-2024
University of Florida
2020
Columbus Oncology and Hematology Associates
2020
University of Basel
2015-2019
University Hospital of Basel
2015-2019
University of Freiburg
2006
Kaiser Permanente Center for Health Research
1980
Kaiser Permanente
1980
Currently used hepatocyte cell systems for in vitro assessment of drug metabolism include hepatoma lines and primary human (PHH) cultures. We investigated the suit-ability validated vivo Basel phenotyping cocktail (caffeine [CYP1A2], efavirenz [CYP2B6], losartan [CYP2C9], omeprazole [CYP2C19], metoprolol [CYP2D6], midazolam [CYP3A4]) characterized four (HepG2 cells, HepaRG cryopreserved hepatocytes 2-dimensional [2D] culture or 3D-spheroid co-culture) regarding basal CYP inducibility. Under...
Metoprolol is used for phenotyping of cytochrome P450 (CYP) 2D6, a CYP isoform considered not to be inducible by inducers the CYP2C, CYP2B and CYP3A families such as rifampicin. While assessing CYP2D6 activity under basal conditions after pretreatment with rifampicin in vivo, we surprisingly observed drop metoprolol/α-OH-metoprolol clearance ratio, suggesting induction. To study this problem, performed vitro investigations using HepaRG cells primary human hepatocytes (before treatment 20 µM...
Activity of human cytochrome P450 enzymes (CYPs) shows high inter-and intra-individual variability, which is determined by genetic and non-genetic factors. Using a combination CYP-specific probe drugs, phenotyping cocktails allow simultaneous assessment the activity different CYP isoforms. The objective this study was to characterize metrics Basel cocktail in healthy male subjects with induced inhibited activity.In randomized crossover study, drugs for CYP1A2 (caffeine), CYP2B6 (efavirenz),...
Though knowledge about physician's assistants and nurse practitioners is far from conclusive, these new health (NHPs) appear to perform a large percentage of primary care services at high level quality productivity. Moreover, the gap between physician/NHP substitution ratio NHP/physician cost seems wide enough assure savings when NHPs are used well.
1. Electrically evoked release of [3H]-noradrenaline ([3H]-NA) or [3H]-5-hydroxytryptamine ([3H]-5-HT) in slices human and the rat neocortex was used to characterize presynaptic opioid receptors. 2. Release [3H]-NA neocortical reduced only by mu-receptor agonist DAMGO (pIC50: 7.27, CI95: [7.22, 7.32]; Imax: 77.6+/-1.6%; antagonized naloxone: pA2: 8.88, [8.78, 8.98]). 3. unaffected DAMGO, but inhibited delta-receptor DPDPE (Imax: 25.7+/-2.2%) kappa-receptor U-50,488H (19.7+/-2.7% inhibition...
For therapeutic drug monitoring in remote settings, dried blood spots (DBS) are particularly advantageous, as sample collection and handling is uncomplicated. The aim of this study was to develop validate an automated extraction method for the analysis nevirapine, efavirenz lopinavir DBS samples. Automated performed with methanol : water (70 30 v/v), using a DBS-MS 500 autosampler coupled liquid chromatography tandem mass spectrometry system. used digital images each position head, sprayed...
Abstract Objective This Phase II, placebo‐controlled, double‐blind study investigated the efficacy, safety, and tolerability of nivasorexant in treatment adults with moderate to severe binge‐eating disorder (BED). Methods Adults meeting DSM‐5 BED criteria were randomized 1:1 placebo or (100 mg b.i.d.). The primary endpoint was change from baseline Week 12 number binge eating (BE) days per week. Exploratory efficacy endpoints included cessation BE last 4 weeks treatment; episodes/week,...
We evaluated whether dried blood spots (DBS) are suitable to monitor combined ART when samples collected in rural Tanzania and transported over a long distance specialized bioanalytical laboratory.Plasma DBS were from study patients treated with nevirapine, efavirenz or lopinavir. In addition, plasma, whole obtained cohort of HIV at the site laboratory Switzerland. analysed using fully automated LC-MS/MS method.Comparison versus plasma concentrations bridging Switzerland indicated an...
Aims We compared the phenotyping metrics of a combination capsule formulation to its individual components newly composed Basel cocktail. Moreover, we investigated reduced sampling regimen for clinical applications. Methods performed in vitro experiments and crossover pharmacokinetic study twelve healthy male subjects compare cocktail containing 6 cytochrome P450 (CYP) probe drugs with administration same drugs. Parent compounds selected metabolites were determined by liquid...
The aim of this study was to evaluate the impact renal impairment on pharmacokinetics (PKs), safety, and tolerability daridorexant, a dual orexin receptor antagonist intended for treatment insomnia. A single-center, open-label evaluated PKs daridorexant in patients with severe function (SRFI; determined by creatinine clearance using Cockcroft-Gault equation; N = 8) not dialysis, matched control subjects (based sex, age, body weight; 7). single oral dose 25 mg orally administered morning....
Objectives Self‐reported adherence assessment in HIV‐infected patients on antiretroviral therapy (ART) is challenging and may overestimate adherence. The aim of this study was to improve the ability health care providers elicit patients’ reports nonadherence using a “patient‐centred” approach rural sub‐Saharan African setting. Methods A prospective interventional cohort ART for ≥ 6 months attending an HIV clinic Tanzania carried out. intervention consisted 2‐day workshop patient‐centred...
Abstract ACT‐539313 is a potent and selective orexin‐1 receptor antagonist. CYP3A the major cytochrome P450 (CYP) enzyme involved in metabolism clearance of man. The main objective this study was to investigate effect on pharmacokinetics orally administered midazolam. Thereby, single‐center, open‐label, fixed‐sequence investigated interaction potential following single‐ (on day 2) repeated‐dose 11) twice‐daily administration 200 mg ACT‐539313. Exposure midazolam higher during concomitant...
Nivasorexant, a selective orexin-1-receptor antagonist, has recently been assessed in the treatment of humans with binge-eating disorder. Herein, inhibitory potential nivasorexant on cytochromes P450 (CYPs) 2C9, 2C19, and 3A4 was evaluated. Human liver microsomes/recombinant CYP enzymes were evaluated vitro. In vivo, single-center, open-label, fixed-sequence study performed healthy adults to explore effect 100 mg administered twice daily (b.i.d.) pharmacokinetics (PK) flurbiprofen (50 mg,...
ACT-1014-6470 is an orally available complement factor 5a receptor 1 antagonist and a novel treatment option in auto-inflammatory diseases. The vitro inhibition potential of on cytochrome P450 isozymes (CYPs) its effect the pharmacokinetics (PK) CYP2C19 CYP3A4 substrates omeprazole midazolam, respectively, humans were assessed. In assays conducted with isoform-specific human liver microsomes. open-label, two-period, fixed-sequence cocktail study, single doses 20 mg 2 midazolam administered...
The vitamin B12 analog hydroxy-cobalamin[c-lactam] (HCCL) impairs hepatic mitochondrial protein synthesis and function of the electron transport chain in rats. We aimed to establish an vivo model for dysfunction mice, which could be used investigate hepatotoxicity toxicants. In a first step, we performed dose-finding study mice treated with HCCL 0.4 mg/kg 4 i.p. two four weeks. plasma methylmalonate concentration was strongly increased at starting three weeks treatment. subsequently daily...