A5004631798- Lipoproteins and Cardiovascular Health
- Respiratory viral infections research
- Computational Drug Discovery Methods
- Diabetes Treatment and Management
- Neonatal Respiratory Health Research
- Biosimilars and Bioanalytical Methods
- Pneumonia and Respiratory Infections
- Pharmacogenetics and Drug Metabolism
- Pharmaceutical Economics and Policy
- Drug-Induced Hepatotoxicity and Protection
- Analytical Chemistry and Chromatography
- Viral gastroenteritis research and epidemiology
- Pharmacological Effects and Assays
- Pharmaceutical studies and practices
- Monoclonal and Polyclonal Antibodies Research
- Advancements in Transdermal Drug Delivery
- Drug Transport and Resistance Mechanisms
- Microbial Metabolism and Applications
- Analytical Methods in Pharmaceuticals
- HIV/AIDS drug development and treatment
- Cystic Fibrosis Research Advances
- Metabolism, Diabetes, and Cancer
- Immunodeficiency and Autoimmune Disorders
- Allergic Rhinitis and Sensitization
- Peroxisome Proliferator-Activated Receptors
Merck & Co., Inc., Rahway, NJ, USA (United States)
2008-2024
United States Military Academy
2000-2024
A series of studies were conducted to explore the mechanism pharmacokinetic interaction between simvastatin (SV) and gemfibrozil (GFZ) reported recently in human subjects. After administration a single dose SV (4 mg/kg p.o.) dogs pretreated with GFZ (75 p.o., twice daily for 5 days), there was an increase (∼4-fold) systemic exposure hydroxy acid (SVA), but not SV, similar observation humans. pretreatment did ex vivo hydrolysis SVA dog plasma. In liver microsomes, exerted minimal inhibitory...
Clesrovimab (MK-1654) is an investigational, half-life extended human monoclonal antibody (mAb) against RSV F glycoprotein in clinical trials as a prophylactic agent infection for infants.This adult study measured clesrovimab concentrations the serum and nasal epithelial lining fluid (ELF) to establish partitioning of after dosing. ELF were normalized sampling dilution using urea from serum. Furthermore, vitro neutralization following dosing was also examine activity compartment.mAbs with...
Abstract Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infection and related morbidity mortality in infants. Passive immunization with an RSV‐neutralizing antibody can provide rapid protection to this vulnerable population. Proof‐of‐concept for approach has been demonstrated by palivizumab; however, use generally restricted highest‐risk infants due monthly dosing requirements its cost. To address large unmet medical need most infants, we are...
A sensitive and reliable procedure for the simultaneous determination of simvastatin (SV) its active beta-hydroxy acid metabolite (SVA) in human plasma was developed validated. The analytes were extracted simultaneously from 0.5 ml aliquots samples by methyl tert-butyl ether (MTBE) via Chem Elut cartridge extraction [also called liquid-solid (LSE) or liquid-liquid (LLCE)], separated through a Kromasil C(18) column (50 x 2 mm i.d. 5 microm) detected tandem mass spectrometry with turbo...
In this paper we show the application of Tasso OnDemand™, a novel automated sample collection device, in conjunction with volumetric absorptive microsampling (VAMS) for development gefapixant, P2X3 receptor antagonist currently under clinical treatment refractory and unexplained chronic cough endometriosis-related pain. A LC–MS/MS bioanalytical method was developed validated using VAMS to support program. This utilized drug–drug interaction study establish mathematical bridging relationship...
Two randomized, two‐period crossover studies were conducted to evaluate the effects of repeat oral dosing troglitazone (Study I) and pioglitazone II) on pharmacokinetics plasma HMG‐CoA reductase inhibitors following multiple doses simvastatin in healthy subjects. In both studies, each subject received two treatments. Treatment A consisted once‐daily 400 mg or 45 for 24 days with coadministration 40 80 Days 15 through 24. B 10 days. Study I, area under concentration‐time profiles (AUC)...
In this study, midazolam was used as a probe‐sensitive CYP3A substrate to investigate the effect of anacetrapib on activity, and ketoconazole probe‐inhibitor potent inhibition pharmacokinetics anacetrapib, novel cholesteryl ester transfer protein inhibitor in development for treatment dyslipidemia. Two partially blinded, randomized, 2‐period, fixed‐sequence studies were performed. Safety, tolerability, plasma concentrations assessed. All treatments generally well tolerated. The geometric...
The Journal of Clinical PharmacologyVolume 49, Issue 4 p. 483-488 Effect Sitagliptin on the Pharmacokinetics Simvastatin Dr Arthur J. Bergman PhD, PhD Merck Research Laboratory, Rahway, New JerseySearch for more papers by this authorMs Josee Cote BS, Ms BS authorDr Andrea Maes Jamie Zhao authorMr Brad A. Roadcap MS, Mr MS Li Sun Robert Valesky Amy Yang Bart Keymeulen MD, Metabolic Unit, Diabetes Center, Free University Brussels and UZ Brussels, BelgiumSearch Zissi Mathijs MD Marina De Smet...
Abstract Background Clesrovimab is an investigational monoclonal antibody with extended half-life targeting site IV of the respiratory syncytial virus (RSV) fusion protein for prevention RSV disease in infants. Methods In this phase 1b/2a, double-blind study, 183 healthy preterm and full-term infants 2 weeks to 8 months age were randomized 4:1 within 5 panels (preterm 20, 50, 75, or 100 mg; mg) receive 1 dose clesrovimab placebo. The objectives evaluate safety, pharmacokinetics, serum...
Aim: A method to quantitate doravirine (MK-1439) in human plasma has been developed support clinical trials designed evaluate the safety, pharmacokinetics and efficacy of compound. Methodology & results: The analyte was extracted using liquid–liquid extraction, separated on a reverse phase HPLC column, detected an API-4000 mass spectrometer Turbo-Ion spray source positive ionization mode coupled with multiple reaction monitoring used for quantification. dynamic range assay 0.02–10 ng/ml 100...
To assess the bioequivalence of an ezetimibe/simvastatin (EZE/SIMVA) combination tablet compared to coadministration ezetimibe and simvastatin as separate tablets (EZE + SIMVA).In this open-label, randomized, 2-part, 2-period crossover study, 96 healthy subjects were randomly assigned participate in each part study (Part I or II), with consisting 2 single-dose treatment periods separated by a 14-day washout. Part consisted Treatments A 10 mg SIMVA mg) B (EZE/SIMVA 10/10 mg/mg) II C 80 D...
BACKGROUND/AIMS MK-0431 (sitagliptin) is a selective DPP-IV inhibitor in Phase III development for the treatment of type 2 diabetes. Since sitagliptin expected to be commonly co-administered with statins, effect on pharmacokinetics (PK) simvastatin, CYP3A4 substrate, was evaluated. METHODS Twelve healthy subjects were randomized periods: (A) single oral dose simvastatin 20 mg and (B) daily doses 200 Days 1 through 5 Day 5. Plasma collected 24 hours following each simvasatin determine PK...
Cholesteryl ester transfer protein (CETP) inhibitor is a target for both lowering low-density lipoproteins and raising high-density lipoproteins. Anacetrapib was the lead compound in our cholesteryl program. Preclinical studies were initiated to support safety of anacetrapib deposition adipose tissue, followed by clinical trial evaluate effects people with vascular disease. An ultra-high performance liquid chromatography/tandem mass spectrometry method developed determine tissue...
Abstract Background MK-1654 is a respiratory syncytial virus (RSV) F glycoprotein neutralizing monoclonal antibody (mAb) with an extended half-life in late development to prevent RSV infection infants. Neutralizing mAbs, like MK-1654, have great potential for prophylaxis against viral infection. However, well-validated approaches clinical dose and efficacy predictions are lacking. Methods Summary-level literature data from prevention studies were used model-based meta-analysis (MBMA)...