C-labeled YH4808, a novel potassium-competitive acid blocker, was intravenously administered as a microtracer at 80 μg (11.8 kBq or 320 nCi) concomitantly with the nonradiolabeled oral drug at 200 mg to determine the absolute bioavailability and to assess the effect of pharmacogenomics on the oral absorption of YH4808. The absolute bioavailability was low and highly variable (mean, 10.1%; range, 2.3-19.3%), and M3 and M8, active metabolites of YH4808, were formed 22.6- and 38.5-fold higher after oral administration than intravenous administration, respectively. The product of the fraction of an oral YH4808 dose entering the gut wall and the fraction of YH4808 passing on to the portal circulation was larger in subjects carrying the variants of the CHST3, SLC15A1, and SULT1B1 genes. A combined LC+AMS is a useful tool to construct a rich and highly informative pharmacokinetic knowledge core in early clinical drug development at a reasonable cost.

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.