Positron emission tomography (PET) is frequently used to obtain target occupancy (%TO) of central nervous system (CNS) drug candidates during clinical development. Obtaining %TO with PET can be particularly powerful when the %TO associated with efficacy is known for a protein target. Using the radiotracer [F]AV-133, the relationship between plasma concentration (PK) and %TO of NBI-750142, an experimental inhibitor of the vesicular monoamine transporter type 2 (VMAT2) was obtained in both nonhuman primate (NHP) and human.
View Article and Find Full Text PDFBackground: Specific antimigraine medications (dihydroergotamine (DHE), triptans) have been associated with adverse pregnancy outcomes in individual studies but lack of consensus remains.
Objectives: Quantify the risk of prematurity, low birth weight (LBW), major congenital malformations (MCM), and spontaneous abortions (SA) associated with gestational use of DHE or triptans in a privately insured cohort of pregnant women in the US.
Methods: We conducted a cohort study within the US Merative MarketScan Research Database (2011-2021), composed of a nationally representative sample of patients with employer-provided health insurance.
Objective: To assess the relationships between dihydroergotamine (DHE) pharmacokinetic (PK) parameters, clinical efficacy, and nausea incidence to determine a DHE PK profile that optimizes efficacy while minimizing adverse events (AEs), particularly nausea.
Background: Dihydroergotamine is a widely used option for the acute treatment of migraine. Although multiple DHE dosage forms, with varying PK and AE profiles, have been evaluated in randomized controlled trials (RCTs), the relationships between PK profile, efficacy, and the common DHE-related AE, nausea, have not been comprehensively evaluated.