A5037239328- Antibiotics Pharmacokinetics and Efficacy
- Antibiotic Resistance in Bacteria
- Pneumonia and Respiratory Infections
- Antimicrobial Resistance in Staphylococcus
- Pharmaceutical studies and practices
- Antifungal resistance and susceptibility
- Antibiotic Use and Resistance
- Veterinary medicine and infectious diseases
- Bacterial Identification and Susceptibility Testing
- Inhalation and Respiratory Drug Delivery
- Biosimilars and Bioanalytical Methods
- Drug Transport and Resistance Mechanisms
- Mycobacterium research and diagnosis
- Pharmacological Effects of Natural Compounds
- Tuberculosis Research and Epidemiology
- Pneumocystis jirovecii pneumonia detection and treatment
- Pharmacological Effects and Toxicity Studies
- Clostridium difficile and Clostridium perfringens research
- Statistical Methods in Clinical Trials
- Fungal Infections and Studies
- Analytical Methods in Pharmaceuticals
- Urinary Tract Infections Management
- SARS-CoV-2 and COVID-19 Research
- Neutropenia and Cancer Infections
- COVID-19 Clinical Research Studies
Institute for Clinical Pharmacodynamics (United States)
2016-2025
John Wiley & Sons (United States)
2023
Hudson Institute
2023
Liechtenstein Institute
2023
Columbus Oncology and Hematology Associates
2018-2021
University at Buffalo, State University of New York
2009-2020
University of Florida
2018
New York University
2015
Cognizant (United States)
2002-2007
Albany Research Institute
2007
Since the advent of modern era antimicrobial chemotherapy in 1930s, animal infection models have allowed for vivo evaluation agents treatment experimentally induced infection. Today, pharmacokinetic-pharmacodynamic (PK-PD) serve as a cornerstone preclinical assessment process antibacterial and dose dosing interval selection, decision support setting vitro susceptibility breakpoints, and, finally, meaning resistance. Over past 15 years, considerable PK-PD data been derived from infected...
The objective of this analysis was to evaluate the relationship between daptomycin exposure and probability an elevation in creatine phosphokinase (CPK) level (hereafter, "CPK elevation") patients with Staphylococcus aureus bacteremia or without infective endocarditis.Phase 3 data for S. bacteremia, endocarditis, who received intravenous (6 mg/kg daily) whom pharmacokinetic were collected evaluated. On basis univariate logistic regression, Bayesian post hoc estimates a CPK Time examined...
Multiple studies of vaccinated and convalescent cohorts have demonstrated that serum neutralizing antibody (nAb) titers correlate with protection against coronavirus disease 2019 (COVID-19). However, the induction multiple layers immunity after severe acute respiratory syndrome 2 (SARS-CoV-2) exposure has complicated establishment nAbs as a mechanistic (CoP) hindered definition protective nAb threshold. Here, we show half-life–extended monoclonal (adintrevimab) provides about 50% symptomatic...
ABSTRACT Pharmacokinetic and clinical data from tigecycline-treated patients with hospital-acquired pneumonia (HAP) who were enrolled in a phase 3 trial integrated order to evaluate pharmacokinetic-pharmacodynamic (PK-PD) relationships for efficacy. Univariable multivariable analyses conducted identify factors associated microbiological responses, based on 61 evaluable HAP received tigecycline intravenously as 100-mg loading dose followed by 50 mg every 12 h minimum of 7 days whom there...
Oritavancin is a novel glycopeptide antimicrobial agent with potent in vitro activity against wide variety of gram-positive bacteria, including multidrug-resistant strains staphylococci and enterococci. A population pharmacokinetic model was developed to describe the disposition oritavancin data from pooled phase 1 healthy subjects 2 3 patients complicated skin structure infections or Staphylococcus aureus bacteremia. In addition, potential influence factors such as subject's age, gender,...
ABSTRACT Oritavancin is a lipoglycopeptide antibiotic with activity against Gram-positive bacteria. Here we describe oritavancin population pharmacokinetics and the impact of patient-specific covariates on drug exposure variability. Concentration-time data were analyzed from two phase 3 clinical trials, SOLO I II, in which was administered as single 1,200-mg dose to patients acute bacterial skin structure infections. A total 1,337 concentrations 297 (90% whom had 4 or 5 pharmacokinetic...
ABSTRACT Meropenem-vaborbactam is a fixed combination of the novel β-lactamase inhibitor vaborbactam and carbapenem antibiotic meropenem, developed for treatment serious infections caused by drug-resistant Gram-negative bacteria. The safety, tolerability, pharmacokinetics (PK) meropenem following single multiple ascending doses each study drug administered alone or combined were evaluated in 76 healthy adult subjects randomized, placebo-controlled, double-blind study. Subjects enrolled 1 5...
Omadacycline, a novel aminomethylcycline with in vitro activity against Gram-positive and -negative organisms, including Streptococcus pneumoniae Haemophilus influenzae, is approved the United States to treat patients community-acquired bacterial pneumonia (CABP). Using nonclinical pharmacokinetic-pharmacodynamic (PK-PD) targets for efficacy surveillance data omadacycline S. H. population pharmacokinetic model, PK-PD target attainment analyses were undertaken using total-drug epithelial...
Despite national guidelines for treatment of hyperlipidemia, significant numbers individuals with coronary artery disease are not treated to their National Cholesterol Education Program (NCEP) low-density lipoprotein (LDL) goals. The potential benefits a clinical pharmacist-managed lipid clinic would be improve rates success in achieving these goals, drug adherence and compliance therapy, reduce cardiovascular events. All patients who had documented history were under the care one...
Dalbavancin is a lipoglycopeptide antibiotic with Gram-positive activity and novel pharmacokinetic (PK) properties that result in prolonged terminal half-life of 15.5 days adults. Once weekly dosing adults phase 3 studies complicated skin structure infections documented dalbavancin exposures associated clinical microbiologic efficacy. PK have not been examined children. The primary objective this open-label, multicenter single-dose 1 study was to characterize the hospitalized pediatric...
Abstract Pharmacokinetics and antithrombotic effects of the Factor Xa inhibitor rivaroxaban were studied in subjects with mild renal insufficiency concurrently taking P‐glycoprotein moderate CYP3A verapamil, a drug commonly administered to patients hypertension, ischemic heart disease, or atrial fibrillation. Age‐matched controls normal function concurrently. Subjects’ overall mean age was 59 years. Mean creatinine clearance values 2 groups 105 71 mL/min. After single 20‐mg oral doses, area...
ABSTRACT Vaborbactam is a member of new class β-lactamase inhibitors with inhibitory activity against serine carbapenemases (e.g., Klebsiella pneumoniae carbapenemase) that has been developed in combination meropenem. The pharmacokinetics the was evaluated 41 subjects chronic renal impairment phase 1, open-label, single-dose study. Subjects were assigned to one five groups based on function: normal (creatinine clearance ≥90 ml/min), mild (estimated glomerular filtration rate [eGFR] 60 89...
ABSTRACT Rezafungin (CD101) is a novel echinocandin antifungal agent with activity against Aspergillus and Candida species, including azole- echinocandin-resistant isolates. The objective of these analyses was to conduct pharmacokinetic (PK)-pharmacodynamic (PD) target attainment evaluate single once-weekly rezafungin dosing provide dose selection support for future clinical studies. Using previously developed population PK model, Monte Carlo simulations were conducted utilizing the...
Although hydromethylthionine is a potent tau aggregation inhibitor, no difference was found in either of two Phase III trials mild to moderate Alzheimer's disease (AD) comparing doses the range 150-250 mg/day with 8 intended as control. To determine how drug exposure related treatment response. A sensitive plasma assay for used population pharmacokinetic analysis samples from 1,162 1,686 patients who participated available and efficacy outcome data. There are steep concentration-response...
Exposure-response analyses for efficacy and safety were performed tigecycline-treated patients suffering from community-acquired pneumonia. Data collected two randomized, controlled clinical trials in which administered a 100-mg loading dose followed by 50 mg of tigecycline every 12 h. A categorical endpoint, success or failure, 7 to 23 days after the end therapy (test cure) continuous time fever resolution, evaluated exposure-response efficacy. Nausea/vomiting, diarrhea, headache, changes...
ABSTRACT The choice of an antimicrobial agent must balance optimization efficacy endpoints with the minimization safety events. risk versus benefit daptomycin for patients Staphylococcus aureus bacteremia or without infective endocarditis receiving at 6, 8, and 10 mg/kg body weight/day was assessed. relationships between area under concentration-time curve over 24 h (AUC)/MIC ratio both clinical response time to decreased susceptibility were evaluated using data from such infections who...
A mathematical model for antiviral clinical trials improves dose selection and understanding of drug-virus interaction.
CD101 is a novel echinocandin with concentration-dependent fungicidal activity in vitro and long half-life (∼133 h humans, ∼70 to 80 mice). Given these characteristics, it likely that the shape of exposure (i.e., time course concentrations) influences efficacy. To test this hypothesis, doses which produce same total area under concentration-time curve (AUC) were administered groups neutropenic ICR mice infected Candida albicans R303 using three different schedules. A dose 2 mg/kg was as...
Rezafungin (CD101) is a novel echinocandin antifungal agent currently in clinical development for the treatment of candidemia and invasive candidiasis. has potent vitro activity against Candida albicans glabrata, including azole- echinocandin-resistant isolates. The objective this analysis was to develop population pharmacokinetic (PK) model characterize disposition rezafungin plasma following intravenous (i.v.) administration. Data from two phase 1 studies, single-ascending-dose study...
Hydromethylthionine is a potent inhibitor of pathological aggregation tau and TDP-43 proteins.To compare hydromethylthionine treatment effects at two doses to determine how drug exposure related response in bvFTD.We undertook 52-week Phase III study 220 bvFTD patients randomized 200 mg/day 8 (intended as control). The principal outcomes were change on the Addenbrookes Cognitive Examination - Revised (ACE-R), Functional Activities Questionnaire (FAQ), whole brain volume. Secondary included...
Use of parenteral amikacin to treat refractory nontuberculous mycobacterial (NTM) lung disease is limited by systemic toxicity. A population pharmacokinetic model was developed using data pooled from two randomized trials evaluate the properties once-daily liposome inhalation suspension (ALIS) in patients with treatment-refractory NTM disease. In phase 2 (TR02-112) and 3 (CONVERT) studies, sputum cultures positive for Mycobacterium avium complex (both studies) or M. abscessus despite ≥ 6...
The use of fluoroquinolones for the treatment community-acquired respiratory tract infection is increasing. Since Streptococcus pneumoniae a ratio 24-h area under concentration-time curve (AUC(24)) agent to MIC (AUC(24)/MIC) greater than 30 fraction unbound drug (f(u)) major pharmacokinetic-pharmacodynamic (PK-PD) parameter correlating with bacterial eradication by in nonclinical models and infected patients, Antimicrobial Resistance Rate Epidemiology Study Team systematically compared vitro...
Tigecycline is a new-generation of tetracycline (glycylcyclines) and active in vitro against bacteria that possess any the classical genes confer resistance through ribosomal protection or efflux pumps. Herein, tigecycline disposition patients with community- hospital-acquired pneumonia was described using population pharmacokinetic model. Additionally, influence covariates, such as body surface area, severity illness, clinical laboratory measures, on evaluated. An intravenous loading dose...
Ceftaroline, the active form of ceftaroline fosamil, is a broad-spectrum cephalosporin antibiotic. A population pharmacokinetic (PPK) model for was developed in NONMEM® using data from 185 healthy subjects and 92 patients with acute bacterial skin structure infection (ABSSSI). Data 128 community-acquired pneumonia (CABP) were used external validation. Healthy received 50-2,000 mg fosamil via intravenous (IV) infusion over 1 hour or intramuscular (IM) injection q12h q24h. ABSSSI CABP 600 IV...