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 [ 14 C]-BI 425809 30 µg. In study 2, participants received an oral dose of [ 14 C]-BI 425809 25 mg containing [ 14 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 [ 14 C]-BI 425809 was 96.7%, with ~ 48% of [ 14 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 [ 14 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. Supplementary Information The online version contains supplementary material available at 10.1007/s40261-021-01111-9.

Suppression of kininogenesis is an adaptive phenomenon in cerebral ischemia/reperfusion in rats aimed at elimination of the no-reflow phenomenon. Hyperkininogenesis and suppression of kinin destruction are pathogenetically significant, because they augment the manifestations of no-reflow phenomenon during reperfusion following ischemia.

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