REMOVED: Pharmacokinetics, mass balance and metabolism of [14C] ADC189, a novel inhibitor of the polymerase acidic protein, in humans

To explore the metabolic mechanism, pharmacokinetic characteristics, and clearance pathways of ADC189 in vivo. In this study, which used a single-center, open, nonrandomized, single-dose trial design. [ 14 C] ADC189 is rapidly absorbed in humans and undergoes O-dealkylation to form [ 14 C] ADC189-I07 (M485b). The metabolite M485b has been reported to exhibit T max was 3.51 h, C max was 57.5 ng/mL, and AUC 0-∞ was 2647 h·ng/mL. In plasma and blood, the mean C max values for radioactivity were 152 and 119 ng eq./mL, respectively, the mean AUC 0-∞ values were 7,373 and 1,011 ng eq./mL·h, respectively, the mean T max values were 3,373 and 1,011 ng eq./mL·h, respectively, the mean T max values were 3.03 and 3.15 h, and the mean t 1/2 values were 40.4 and 11.6 h, respectively. Based on the results of the metabolite profile, and metabolite structure analyses of the urine and fecal samples, it was hypothesized that the main clearance pathways of ADC189 in the human body after a single dose of the drug are as follows: the prodrug ADC189 is metabolized and excreted via several pathways: it can be O-dealkylated to form M485b (excreted in feces and urine), glucuronidated to form M661 (excreted in urine), oxidized to form M501a/b (excreted in feces and urine), or deoxygenated to form M457 (excreted in feces). The results of this study collectively indicate that [ 14 C]ADC189 does not significantly bind to blood cells, and its primary excretion route is fecal excretion, while urinary excretion is a secondary route.