Publications by authors named "John David Clements"
Background And Objectives: Blinatumomab (BLINCYTO) is a novel bispecific T cell engager (BiTE) approved in the USA for the treatment of relapsed or refractory B cell precursor acute lymphoblastic leukemia (ALL) in children and adults, as well as minimal residual disease ALL in adults. This analysis characterized the population pharmacokinetics of intravenous blinatumomab in pediatric and adult patients.
Methods: A total of 2417 serum concentrations of blinatumomab from 674 patients, including adult (n = 628) and pediatric patients (n = 46), from eight clinical studies were analyzed.
Receiver Operating Characteristic Analysis and Clinical Trial Simulation to Inform Dose Titration Decisions.
CPT Pharmacometrics Syst Pharmacol
November 2018
Article Synopsis
- Optimal dose selection in clinical trials faces challenges when effective and toxic concentrations are similar, prompting the development of a novel quantitative approach for dose titration.
- A simulation system incorporating pharmacokinetics, pharmacodynamics, and varying types of variability was used to test different scenarios in optimizing drug titration while balancing efficacy and safety.
- The approach significantly reduced toxicity rates by 87.4% to 93.5% and increased efficacy by 52.7% to 243%, suggesting that interindividual variability may be less critical than other forms of variability in determining optimal dosing strategies.
Inflammatory conditions reduce the potency to prolong the PR interval of certain cardiovascular drugs including propranolol, sotalol, and verapamil in rats and humans despite elevated plasma drug concentrations. We tested whether pravastatin restores altered action and disposition of propranolol as well as inflammatory mediators concentrations in the Pre-Adjuvant Arthritis (Pre-AA) Sprague-Dawley rat model. Rats [Healthy/Placebo, Arthritis/Placebo, Healthy/Statin, and Arthritis/Statin groups (n=14-16/group)] received Mycobacterium butyricum on day 0 followed by 6 mg/kg pravastatin or placebo twice daily during days 4-8.
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