Metabolism and Excretion of GCC-4401C, a Factor Xa Inhibitor, in Humans

Abstract

Aim: This study investigated the pharmacokinetics, excretion and metabolism of [14 C]-GCC-4401C, a factor Xa inhibitor, using a microtracer approach. Results/ methodology: Total [14 C] in excreta and plasma, and radiochromatographic profiles were determined using accelerator MS and liquid scintillation counting. LC/MS was used to assess pharmacokinetics and metabolism. The average plasma exposure for [ 14 C] was higher than for GCC-4401C, indicating that metabolites with a longer halflife than GCC-4401C were formed. Mean total recovery of [ 14 C] in urine and feces was 87.3%. GCC-4401C was the primary contributor (58%) to total radioactivity in plasma. A total of 12 metabolites were identified; M11 and M12 were the major circulating metabolites. The major metabolic routes of GCC-4401C in humans were oxidation and dehydrogenation. Discussion/conclusion: The study successfully assessed the elimination and metabolism of GCC-4401C.

Absorption, Metabolism, and Excretion of ACT-1004-1239, a First-In-Class CXCR7 Antagonist: In Vitro, Preclinical, and Clinical Data

“…However, the geometric means of AUC 0-∞ and terminal t 1/2 of total 14 C-radioactivity were approximately 2-fold higher than the ones of 100 mg non-radioactive ACT-1004-1239. This suggests that the metabolism of ACT-1004-1239 in humans results in metabolites, which have a lower elimination rate, and thus, cause the increase in AUC 0-∞ and t 1/2 as previously observed ( Roffel et al, 2017 ; Muehlan et al, 2019 ). Following oral administration of 9.2 μg 14 C-ACT-1004-1239, the mean cumulative recovery of radioactivity in urine and feces was approximately 84%, which is above the generally acceptable threshold for human ADME studies (>80%) ( Roffey et al, 2007 ).…”