A phase I, open-label, single-dose micro tracer mass balance study of C-labeled ASP7991 in healthy Japanese male subjects using accelerator mass spectrometry.

ASP7991 is a calcimimetic that acts on the calcium-sensing receptor on parathyroid cell membranes and suppresses parathyroid hormone (PTH) secretion in the treatment of secondary hyperparathyroidism. The mass balance and metabolite profile of [C]ASP7991 were investigated in six healthy male subjects after a single oral dose of [C]ASP7991 [1 mg, 18.5 kBq (500 nCi)] in solution. [C] radioactivity in plasma, urine and feces was analyzed using Accelerator mass spectrometry. ASP7991 was rapidly absorbed, metabolized and excreted. Mean recovery of [C] radioactivity in urine and feces was 30.08% and 49.31%, respectively, and mean total recovery of [C] radioactivity was 79.39%. The majority of [C] radioactivity in urine and feces was excreted within the first 72 h following administration. Seven metabolites were detected in plasma, urine and feces samples, and their structures were determined by mass spectrometry. The main metabolic pathways of ASP7991 in humans were predicted to be N-dealkylation, followed by N-acetylation and taurine conjugation to a carboxylic acid moiety. Our findings show that a mass balance study using micro radioactivity doses is suitable for elucidating the pharmacokinetics of the absorption, metabolism and excretion of administered drugs.