Track topics on Twitter Track topics that are important to you
Eptinezumab is a humanized mAb that targets calcitonin gene-related peptide and is under regulatory review for the prevention of episodic and chronic migraine (EM, CM). It is important to determine whether exposures achieved with intravenous (IV) administration of eptinezumab achieve desired pharmacologic effects. Population pharmacokinetics, including dose- and exposure-response analyses, were performed using patient-level data from the eptinezumab clinical trial program with IV doses ranging from 10 to 1000 mg in pharmacokinetic analyses or 10 to 300 mg in phase 2/3 clinical studies in patients with EM or CM. Exposure-response analysis explored the relationship between eptinezumab exposure metrics and efficacy parameters including monthly migraine days. The pharmacokinetic profile of eptinezumab was characterized by rapid attainment of maximum plasma concentration (ie, end of IV administration) and a terminal half-life of 27 days. Covariate analysis found that patient characteristics had no clinically significant effects on pharmacokinetic parameters and were insufficient to influence dosing. Dose- and exposure-response analyses found exposure with single doses ≥100 mg was associated with greater efficacy compared with doses ≤30 mg and a plateau of effect between 100 and 300 mg. A saturable inhibitory E model found the exposure over 12 weeks produced by single-dose eptinezumab 100 and 300 mg exceeded the exposure estimates required to achieve 90% of the maximal efficacy (EC ). This pharmacokinetic analysis of eptinezumab supports dosing every 12 weeks with no adjustment for patient characteristics, including exposures associated with 100- or 300-mg doses producing optimal efficacy effects. The similar efficacy profiles support 100 mg as the lowest effective dose of eptinezumab.
This article was published in the following journal.
Name: Pharmacology research & perspectives
High-dose methotrexate (HD-MTX) is widely used in pediatric and adult oncology treatment regimens. This study aimed to develop a population pharmacokinetic model to characterize pediatric and adult MT...
Guanfacine hydrochloride extended-release tablet (GXR) is approved for child and adolescent patients with attention-deficit/hyperactivity disorder (ADHD). The aims of this study were to develop a popu...
Isoniazid (INH) is a first-line antituberculosis (TB) agent with a pharmacokinetic profile characterized by high interindividual variation; however, population pharmacokinetic studies in patients with...
Population Pharmacokinetics and Exposure Response Analysis of Pomalidomide in Subjects With Relapsed or Refractory Multiple Myeloma From the Novel Combination Treatment of Pomalidomide, Bortezomib, and Low-Dose Dexamethasone.
Multiple myeloma is an incurable progressive neoplastic disease that accounts for 10% of all hematologic malignancies. Even though significant progress has been made in the treatment of newly diagnose...
In recent years new targeted small molecule kinase inhibitors (KI) have become available for pediatric patients with cancer. Relationships between drug exposure and treatment response have been establ...
This will be a parallel group, double-blind, randomized, placebo-controlled study assessing the efficacy of eptinezumab for acute migraine, defined as an active intercurrent migraine occur...
An evaluation of long term safety of repeat ALD403 doses in Chronic Migraine
Anxiety disorders affect over a quarter of the population, yet very little is known about the variables that predict treatment outcome. The planned study explores whether a patient's respo...
Talaromycosis continues to be a common opportunistic fungal infection among people living with HIV/AIDS (PLWHA) in Southeast Asia and remains a leading cause of death among this population...
Several population pharmacokinetic (PK) models for cefepime in critically ill patients have been described, all indicating that variability in renal clearance is the main determinant of ob...
A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function.
The maximum exposure to a biologically active physical or chemical agent that is allowed during an 8-hour period (a workday) in a population of workers, or during a 24-hour period in the general population, which does not appear to cause appreciable harm, whether immediate or delayed for any period, in the target population. (From Lewis Dictionary of Toxicology, 1st ed)
Infiltration of inflammatory cells into the parenchyma of PROSTATE. The subtypes are classified by their varied laboratory analysis, clinical presentation and response to treatment.
Ongoing scrutiny of a population (general population, study population, target population, etc.), generally using methods distinguished by their practicability, uniformity, and frequently their rapidity, rather than by complete accuracy.
An internationally recognized set of published rules used for evaluation of cancer treatment that define when tumors found in cancer patients improve, worsen, or remain stable during treatment. These criteria are based specifically on the response of the tumor(s) to treatment, and not on the overall health status of the patient resulting from treatment.
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...
Neurology - Central Nervous System (CNS)
Alzheimer's Disease Anesthesia Anxiety Disorders Autism Bipolar Disorders Dementia Epilepsy Multiple Sclerosis (MS) Neurology Pain Parkinson's Disease Sleep Disorders Neurology is the branch of me...