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Clinical Drug Investigation Jan 2022BACKGROUND AND OBJECTIVES: BI 425809, a novel glycine transporter-1 inhibitor, may ameliorate cognitive deficits in schizophrenia. The objectives of the studies were:...
The Absolute Bioavailability, Absorption, Distribution, Metabolism, and Excretion of BI 425809 Administered as an Oral Dose or an Oral Dose with an Intravenous Microtracer Dose of [C]-BI 425809 in Healthy Males.
UNLABELLED
BACKGROUND AND OBJECTIVES: BI 425809, a novel glycine transporter-1 inhibitor, may ameliorate cognitive deficits in schizophrenia. The objectives of the studies were: to assess absolute bioavailability of oral BI 425809 compared with intravenous (IV) microtracer infusion (study 1), and to determine the mass balance, distribution, metabolism, and excretion of BI 425809 (study 2).
METHODS
These were Phase I, open-label, non-randomized, single-period, single-arm studies in healthy males. Study 1 administered a single oral dose of unlabeled BI 425809 25 mg, then an IV microtracer infusion of [C]-BI 425809 30 µg. In study 2, participants received an oral dose of [C]-BI 425809 25 mg containing [C]-labeled (dose: 3.7 megabecquerel (0.41 mSv)) and unlabeled drug. Safety was assessed.
RESULTS
In study 1 (n = 6), the absolute bioavailability of a 25 mg tablet of BI 425809 in a fasted state was 71.64%. The geometric mean dose-normalized maximum plasma concentration was approximately 80% lower after oral administration versus IV dose. In study 2 (n = 6), the total recovery of [C]-BI 425809 was 96.7%, with ~ 48% of [C]-radioactivity excreted in urine and ~ 48% excreted in feces. Among the labeled drug in urine, ~ 45% of the amount excreted was composed of BI 425809 (17.4%) and two metabolites (BI 758790, 21.0%; BI 761036, 5.9%). In feces, < 1% of BI 425809 was excreted as unchanged drug. In both studies, BI 425809 was generally well tolerated.
CONCLUSIONS
After normalization, the absolute bioavailability of tablet-form BI 425809 was 71.64%. The total recovery of [C]-BI 425809 25 mg was high (96.7%), with low intraindividual variability and similar amounts excreted in urine and feces. CLINICALTRIALS.
GOV IDENTIFIERS
NCT03783000 and NCT03654170.
Topics: Administration, Intravenous; Administration, Oral; Biological Availability; Humans; Male; Organic Chemicals
PubMed: 34936055
DOI: 10.1007/s40261-021-01111-9 -
European Radiology Oct 2023To assess the evolution of administered radiotracer activity for F-18-fluorodeoxyglucose (18F-FDG) PET/CT or PET/MR in pediatric patients (0-16 years) between years 2000...
OBJECTIVES
To assess the evolution of administered radiotracer activity for F-18-fluorodeoxyglucose (18F-FDG) PET/CT or PET/MR in pediatric patients (0-16 years) between years 2000 and 2021.
METHODS
Pediatric patients (≤ 16 years) referred for 18F-FDG PET/CT or PET/MR imaging of the body during 2000 and 2021 were retrospectively included. The amount of administered radiotracer activity in megabecquerel (MBq) was recorded, and signal-to-noise ratio (SNR) was measured in the right liver lobe with a 4 cm volume of interest as an indicator for objective image quality. Descriptive statistics were computed.
RESULTS
Two hundred forty-three children and adolescents underwent a total of 466 examinations. The median injected 18F-FDG activity in MBq decreased significantly from 296 MBq in 2000-2005 to 100 MBq in 2016-2021 (p < 0.001), equaling approximately one-third of the initial amount. The median SNR ratio was stable during all years with 11.7 (interquartile range [IQR] 10.7-12.9, p = 0.133).
CONCLUSIONS
Children have benefited from a massive reduction in the administered 18F-FDG dose over the past 20 years without compromising objective image quality.
CLINICAL RELEVANCE STATEMENT
Radiotracer dose was reduced considerably over the past two decades of pediatric F-18-fluorodeoxyglucose PET/CT and PET/MR imaging highlighting the success of technical innovations in pediatric PET imaging.
KEY POINTS
• The evolution of administered radiotracer activity for F-18-fluorodeoxyglucose (18F-FDG) PET/CT or PET/MR in pediatric patients (0-16 years) between 2000 and 2021 was assessed. • The injected tracer activity decreased by 66% during the study period from 296 megabecquerel (MBq) to 100 MBq (p < 0.001). • The continuous implementation of technical innovations in pediatric hybrid 18F-FDG PET has led to a steady decrease in the amount of applied radiotracer, which is particularly beneficial for children who are more sensitive to radiation.
PubMed: 37855853
DOI: 10.1007/s00330-023-10319-6