A5087532065- Pharmacogenetics and Drug Metabolism
- Pharmacological Effects and Toxicity Studies
- SARS-CoV-2 and COVID-19 Research
- Immunotherapy and Immune Responses
- Chemokine receptors and signaling
- Blood disorders and treatments
- Neurological disorders and treatments
- COVID-19 Clinical Research Studies
- Analytical Methods in Pharmaceuticals
- Parkinson's Disease Mechanisms and Treatments
- Inflammatory mediators and NSAID effects
- Drug Transport and Resistance Mechanisms
- Inflammatory Myopathies and Dermatomyositis
- Neonatal Health and Biochemistry
- Eicosanoids and Hypertension Pharmacology
- Drug-Induced Hepatotoxicity and Protection
- Glycogen Storage Diseases and Myoclonus
- Pharmaceutical studies and practices
- Hormonal Regulation and Hypertension
- Respiratory viral infections research
- Cystic Fibrosis Research Advances
- Epilepsy research and treatment
- Atrial Fibrillation Management and Outcomes
- Genetic Syndromes and Imprinting
- Neurogenetic and Muscular Disorders Research
Hadassah Medical Center
2016-2025
Hebrew University of Jerusalem
2000-2023
Riley Hospital for Children
2023
Indiana University – Purdue University Indianapolis
2023
University Medical Center
2016-2022
Institut de Myologie
2019
Assistance Publique – Hôpitaux de Paris
2019
Sorbonne Université
2019
Children's Hospital of Eastern Ontario
2019
University of Ottawa
2019
New treatments are needed to reduce the risk of progression coronavirus disease 2019 (Covid-19). Molnupiravir is an oral, small-molecule antiviral prodrug that active against severe acute respiratory syndrome 2 (SARS-CoV-2).
Warfarin anticoagulation effect is characterized by marked variability, some of which has been attributed to CYP2C9 polymorphisms. This study prospectively examines whether a priori knowledge genotype may improve warfarin therapy. Patients were randomly assigned receive validated algorithm (“control”, 96 patients) or genotype-adjusted algorithms (“study”, 95 patients). The first therapeutic international normalized ratio and stable reached 2.73 18.1 days earlier in the group, respectively...
Objective Our objective was to investigate population differences in the metabolic activity of cytochrome P450 (CYP) 2C9 between genotypically matched Caucasian and Japanese patients by using unbound oral clearance S ‐warfarin as an vivo phenotypic trait measure. Methods Ninety 47 receiving maintenance warfarin therapy were studied. Steady‐state plasma concentrations measured a chiral HPLC method coupled with ultrafiltration technique, for estimated. By combining urinary excretion rates...
BACKGROUND: Safe and effective oral treatments are needed to improve clinical outcomes for nonhospitalized patients with Covid-19. Molnupiravir is an orally administered, small-molecule ribonucleoside prodrug shown inhibit replication of severe acute respiratory syndrome coronavirus 2 in vitro animal models. METHODS: MOVe-OUT ongoing, phase 2/3, randomized, placebo-controlled, double-blind study evaluating the safety, efficacy, pharmacokinetics molnupiravir adults. In component, participants...
To define the differences in codeine pharmacodynamics extensive (EMs) and poor (PMs) metabolizers of debrisoquin to determine whether inhibition codeine's metabolism by quinidine produces phenotypically dependent pharmacodynamic changes, we studied 16 healthy nonsmoking males, 10 EMs 6 PMs debrisoquin. The subjects received random double-blind fashion 120 mg plus placebo, 100 placebo. Blood was obtained over 24 hr urine collected for 48 hr. Respiratory, psychomotor pupillary effects were...
To investigate the efficacy and safety of aceneuramic acid extended-release (Ace-ER), a treatment intended to replace deficient sialic acid, in patients with GNE myopathy.UX001-CL301 was phase 3, double-blind, placebo-controlled, randomized, international study evaluating Ace-ER myopathy. Participants who could walk ≥200 meters 6-minute test at screening were randomized 1:1, stratified by sex, receive 6 g/d or placebo for 48 weeks assessed every 8 weeks. The primary endpoint change muscle...
Abstract Background Malfunction of astrocytes is implicated as one the pathological factors ALS. Thus, intrathecal injection healthy in ALS can potentially compensate for diseased astrocytes. AstroRx® an allogeneic cell-based product, composed and functional human derived from embryonic stem cells. was shown to clear excessive glutamate, reduce oxidative stress, secrete various neuroprotective factors, act immunomodulator. Intrathecal animal models slowed disease progression extended...
IntroductionND0612 is a continuous, subcutaneous levodopa/carbidopa delivery system under development for patients with Parkinson's disease (PD) and motor fluctuations.MethodsThis was randomized, placebo-controlled, double-blind, 2-period study evaluating the safety pharmacokinetics of ND0612 in PD on an optimized oral levodopa regimen experiencing ≥2 h/day OFF time. During Period-1, received their current standard care (SoC) were randomized (2:1) to 14 days treatment adjunct (daily dose...
The emergence of rapidly spreading variants severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a major challenge to the ability vaccines and therapeutic antibodies provide immunity. These contain mutations specific amino acids that might impede vaccine efficacy. BriLife
Pneumococcal diseases (PD) cause considerable morbidity and mortality in adults. V116 is an investigational 21-valent pneumococcal conjugate vaccine (PCV) specifically designed to protect adults from serotypes responsible for the majority of residual PD. This phase 3 study evaluated safety, tolerability, immunogenicity vaccine-experienced ≥50 years.
Pre-specified interim analyses allow for more timely evaluation of efficacy or futility, potentially accelerating decision-making on an investigational intervention. In such analysis, the randomized, double-blind MOVe-OUT trial demonstrated superiority molnupiravir over placebo outpatient treatment COVID-19 in high-risk patients. full analysis population, point estimate difference primary endpoint was notably lower than at analysis. We conducted a comprehensive assessment to investigate this...
Background: V116 is a 21-valent pneumococcal conjugate vaccine (PCV) designed for adults. It contains the most prevalent serotypes associated with invasive disease (IPD) in adults regions established pediatric vaccination programs. This Phase 3 study compared safety, tolerability, and immunogenicity of 23-valent polysaccharide (PPSV23) ≥50 years age. Methods: In this randomized, active comparator-controlled, parallel-group, multisite, double-blind study, participants were randomized 1:1 to...
CYP2D6 is polymorphically distributed so that in poor metabolizers enzyme activity missing. The goal of this study was to compare the pharmacokinetics and pharmacodynamics codeine with without quinidine between Caucasian Chinese extensive debrisoquin. Nine Caucasians eight subjects received random, double blind fashion, on two occasions, 120 mg. placebo or 100 Pharmacodynamic effects were determined over 6 h. Codeine-apparent clearance partial metabolic by O-demethylation significantly...
Background: GNE Myopathy (GNEM) is a progressive adult-onset myopathy likely caused by deficiency of sialic acid (SA) biosynthesis.Objective: Evaluate the safety and efficacy SA (delivered aceneuramic extended-release [Ace-ER]) as treatment for GNEM.Methods: A Phase 2, randomized, double-blind, placebo-controlled study evaluating Ace-ER 3 g/day or 6 versus placebo was conducted in GNEM subjects (n = 47).After first 24 weeks, crossed over to additional weeks (dose pre-assigned during initial...
Purpose: The potential of the high-affinity CXCR4 antagonist BL-8040 as a monotherapy-mobilizing agent and its derived graft composition quality were evaluated in phase I clinical study healthy volunteers (NCT02073019).Experimental Design: first part was randomized, double-blind, placebo-controlled dose escalation phase. second an open-label phase, which 8 subjects received single injection (1 mg/kg) approximately 4 hours later underwent standard leukapheresis procedure. engraftment purified...
Objectives To compare the effect of omeprazole, a substrate and inhibitor CYP2C19, on diazepam metabolism in white Chinese subjects. Subjects Methods The study, which took place at clinical research center University Hospital, was designed as double blind, crossover, two-stage study; each stage lasted 21 days separated by 4 weeks. were eight seven men who extensive metabolizers debrisoquin mephenytoin. subjects received, randomized order, 40 mg/day, placebo for days, followed 10 mg oral dose...
While treatment with levodopa remains the cornerstone of Parkinson's disease (PD) management, chronic oral therapy is often associated development motor complications, that correlate to fluctuating plasma concentrations, limiting its clinical utility. Continuous infusion considered be optimal delivery route for treating PD patients fluctuations, but current systems require invasive surgery. Subcutaneous (SC) has potential provide a better tolerated and more convenient continuous delivery....
CYP2C9 mediates the oxidative metabolism of approximately 10% drugs, some which are characterized by a narrow therapeutic index. We aimed to validate genotype method and phenotype methodology, for evaluation activity in vivo. Thirty-one healthy subjects (22 male) received single 300 mg dose phenytoin. Blood was drawn periodically urine collected at intervals 96 h. Plasma phenytoin 5-(4-hydroxyphenyl)-5-phenylhydantoin (p-HPPH) S R enantiomers p-HPPH were determined high-performance liquid...
Objectives To compare the pharmacokinetics and dynamics of omeprazole in white Chinese subjects. Methods This double-blind two-stage study, performed clinical research center a university hospital, evaluated 15 healthy nonsmoking men (eight subjects seven extensive metabolizers mephenytoin). Blood samples were obtained over 24 hours after eighth dose (40 mg/day). Omeprazole, sulfone, hydroxyomeprazole calculated from respective plasma concentration-time curves. Twelve- 24-hour integrated...