A5041695667- HIV/AIDS drug development and treatment
- HIV Research and Treatment
- Pneumocystis jirovecii pneumonia detection and treatment
- Biochemical and Molecular Research
- Psoriasis: Treatment and Pathogenesis
- Hepatitis C virus research
- Asthma and respiratory diseases
- Pharmacogenetics and Drug Metabolism
- Pharmacological Effects and Toxicity Studies
- Pharmaceutical studies and practices
- Dermatology and Skin Diseases
- Chronic Lymphocytic Leukemia Research
- Drug Transport and Resistance Mechanisms
- HIV/AIDS Research and Interventions
- HIV-related health complications and treatments
- Phosphodiesterase function and regulation
- Immune Response and Inflammation
- Antibiotics Pharmacokinetics and Efficacy
- Chemokine receptors and signaling
- Medical and Biological Ozone Research
- Cytokine Signaling Pathways and Interactions
- Drug-Induced Adverse Reactions
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Urticaria and Related Conditions
- Chemical Synthesis and Analysis
Merck & Co., Inc., Rahway, NJ, USA (United States)
2013-2023
Thomas Jefferson University
2023
University of Florida
2018
Columbus Oncology and Hematology Associates
2018
LungenClinic Grosshansdorf
2009
SCH527123 is a novel, selective CXC chemokine receptor 2 antagonist that inhibits neutrophil activation and modulates trafficking in animal models, characteristics may be beneficial the treatment of conditions with unbalanced pulmonary neutrophilia, such as chronic obstructive disease. The purpose this proof-of-principle study was to determine whether ozone-induced recruitment healthy humans. In randomised, double-blind, placebo-controlled, three-way crossover study, oral (50 mg once daily,...
GPR109A is not the target mediating niacin’s lipid efficacy and free fatty acid hypothesis does explain mechanism of action.
Absorption, distribution, metabolism and elimination of doravirine (MK-1439), a novel non-nucleoside reverse transcriptase inhibitor, were investigated. Two clinical trials conducted in healthy subjects: an oral single dose [14 C]doravirine (350 mg, ∼200 µCi) trial (n = 6) intravenous (IV) single-dose (100 µg) 12). In vitro metabolism, protein binding, apparent permeability P-glycoprotein (P-gp) transport studies to complement the trials.Following administration, all administered was...
ABSTRACT Doravirine is a novel, highly potent, nonnucleoside reverse transcriptase inhibitor that administered once daily and in development for the treatment of HIV-1 infection. In vitro clinical data suggest doravirine unlikely to cause significant drug-drug interactions via major drug-metabolizing enzymes or transporters. As common infection comorbidity, hypercholesterolemia often treated with statins, including commonly prescribed atorvastatin. Atorvastatin subject cytochrome P450 3A4...
Abstract Tildrakizumab, a high‐affinity humanized IgG1k antibody that selectively binds interleukin (IL)‐23 p19 subunit of cytokine IL‐23 and neutralizes its function, is under investigation for treatment moderate‐to‐severe chronic plaque psoriasis. The objective this analysis was to assess the pharmacokinetics, bioavailability safety/tolerability single ascending doses tildrakizumab after intravenous (IV) subcutaneous (SC) dosing in healthy subjects. P05661 phase 1, single‐dose, randomized,...
Abstract Doravirine is a nonnucleoside reverse transcriptase inhibitor in clinical development for the treatment of human immunodeficiency virus‐1 infection combination with other antiretroviral therapies. The cytochrome P450 (CYP)3A‐dependent metabolism doravirine makes it susceptible to interactions modulators this pathway, including antituberculosis rifampin. Rifabutin, an alternative antibiotic used treat tuberculosis, may have lower‐magnitude effect on CYP3A. aim trial was determine...
Tildrakizumab, an interleukin (IL)-23 inhibitor, is indicated for the treatment of moderate to severe chronic plaque psoriasis. Although tildrakizumab not metabolized by, and does alter, cytochrome P450 (CYP) expression in vitro, clinically significant pharmacokinetic effects through changes systemic inflammation, which alters CYP metabolism, have been well documented. At time study conduct, effect modulation inflammation/cytokines, including IL-23 inhibition with tildrakizumab, on therefore...
ABSTRACT Doravirine is a novel, potent nonnucleoside reverse transcriptase inhibitor (NNRTI) for the treatment of patients with human immunodeficiency virus type 1 (HIV-1) infection that demonstrates high genetic barrier to resistance and has been well tolerated in studies date. candidate switching from less-well-tolerated NNRTIs, such as efavirenz. While doravirine cytochrome P450 3A4 (CYP3A4) substrate, efavirenz induces CYP3A4; therefore, pharmacokinetics both drugs following switch were...
Identifying and understanding potential drug-drug interactions (DDIs) are vital for the treatment of human immunodeficiency virus type 1 (HIV-1) infection. This article discusses DDIs between doravirine, a nonnucleoside reverse transcriptase inhibitor (NNRTI), cytochrome P450 3A (CYP3A) substrates drugs that modulate CYP3A activity. Consistent with previously published in vitro data DDI trials midazolam atorvastatin, doravirine did not have any meaningful impact on pharmacokinetics ethinyl...
Doravirine is a novel nonnucleoside reverse transcriptase inhibitor in development for use with other antiretroviral therapies to treat human immunodeficiency virus type 1 (HIV-1) infection. metabolism predominantly occurs via cytochrome P450 3A <10% of elimination occurring the renal pathway.
Doravirine is a novel, potent, nonnucleoside reverse-transcriptase inhibitor currently in development for HIV-1 infection treatment. As substrate CYP3A-mediated metabolism, doravirine could potentially be affected by liver-function changes. portion of the HIV-1-infected population has varying degrees liver impairment, we investigated effect moderate hepatic impairment on pharmacokinetic profile and tolerability single-dose 100 mg otherwise healthy subjects. A total 16 subjects aged 44–64...
Aims The aim of the studies was to characterize pharmacokinetics desloratadine in healthy children and determine appropriate dose for paediatric patients 2–11 years old. Methods Two open‐label, single‐dose were carried out between 2–5 ( n = 18) 6–11 old 18). On day 1, subjects received a single oral syrup (1.25 mg year olds or 2.5 olds). Subjects followed an additional 4 days during which vital signs measured daily blood samples collected periodically. Results Plasma C max occurred at median...
To evaluate the effect of ethnicity on pharmacokinetics (PK) tildrakizumab, a novel anti-IL-23 monoclonal antibody for treatment psoriasis.This was an open-label, 2-part study in healthy adult subjects. In part 1, Japanese subjects and matched Caucasian Chinese (to Japanese) were assigned to 1 3 cohorts administered tildrakizumab 50, 200, or 400 mg subcutaneously (SC). 2, received 10 mg/kg IV. Pre- post-treatment antidrug antibodies assessed. Safety tolerability assessed throughout study.59...
Doravirine is a non-nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus type 1 (HIV-1) infection. Due to high prevalence HIV-1 and hepatitis C (HCV) coinfection coadministration HCV treatment, potential drug-drug interactions (DDIs) between doravirine two treatments were investigated in phase drug interaction trials healthy participants. Trial effect multiple-dose elbasvir + grazoprevir (N = 12), trial 2 single-dose ledipasvir-sofosbuvir 14). had no...
Abstract Doravirine is a novel non‐nucleoside reverse transcriptase inhibitor indicated for the treatment of human immunodeficiency virus type 1 infection. Because potential concomitant administration with acid‐reducing agents, drug‐interaction trial was conducted to evaluate impact these types medications on doravirine pharmacokinetics. In an open‐label, 3‐period, fixed‐sequence trial, healthy adult participants received following: period 1, single dose 100 mg; 2, coadministration mg and...
What is known and objective Doravirine a non-nucleoside reverse transcriptase inhibitor indicated for the treatment of human immunodeficiency virus (HIV)-1 infection. This phase 1 study in healthy adults investigated pharmacokinetics, safety tolerability long-acting parenteral (LAP) microsuspension formulations doravirine administered as an intramuscular (IM) injection. Methods After confirmation oral doravirine, 36 participants were randomized 1:1:1 to receive IM 200 mg Treatment A (1 × mL,...
Abstract Doravirine, a novel nonnucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus 1 (HIV‐1), is predominantly cleared by cytochrome P450 (CYP) 3A4 and metabolized to an oxidative metabolite (M9). Coadministration with rifabutin, moderate CYP3A4 inducer, decreased doravirine exposure. Based on nonparametric superposition modeling, dose adjustment from 100 mg once daily twice during rifabutin coadministration was proposed. However, M9 exposure may...