A phase I,open-label,single-dose micro tracer mass balance study of 14C-labeled ASP7991 in healthy Japanese male subjects using accelerator mass spectrometry |
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| Institution: | 1. Clinical Pharmacology, Astellas Pharma Inc., 2-5-1 Nihonbashi-Honcho Chuo-ku, Tokyo, 103-8411, Japan;2. Analysis & Pharmacokinetics Research Labs., Astellas Pharma Inc., 21 Miyukigaoka Tsukuba-shi, Ibaraki, 305-8585, Japan;3. Research Program Management, Astellas Pharma Inc., 21 Miyukigaoka Tsukuba-shi, Ibaraki, 305-8585, Japan;1. Amrita Institute of Medical Sciences and Research Center, Amrita Viswavidhyapeetham, Kerala, India;2. WHO RNTCP Technical Assistance Project, WHO Country Office, India;3. Project Director, Kerala State AIDS Control Society, India;4. Dean Hospital, Punalur, Kerala, India;1. Departments of Biomedical Imaging, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia;2. Departments of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia;3. Departments of Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia;4. University of Malaya Research Imaging Centre, University of Malaya, 50603 Kuala Lumpur, Malaysia;5. Radiological and Imaging Sciences and Nottingham Digestive Diseases Biomedical Research Unit, Department of Medical Physics, University of Nottingham, A Floor, Medical School, Queen?s Medical Centre, Nottingham, NG7 2UH, United Kingdom;1. Institute of Pharma Technology, School of Life Sciences, University of Applied Sciences Northwestern Switzerland, Muttenz, Switzerland;2. Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland;3. Alpinia Laudanum Institute of Phytopharmaceutical Sciences AG, Walenstadt, Switzerland;1. Nanotechnology Application Centre, University of Allahabad, Allahabad 211002, India;2. Physics Department, University of Allahabad, Allahabad 211002, India;3. Division of Electronics Engineering, Chonbuk National University, Jeonju, Jeonbuk 561-756, South Korea |
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| Abstract: | 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 14C]ASP7991 were investigated in six healthy male subjects after a single oral dose of 14C]ASP7991 1 mg, 18.5 kBq (500 nCi)] in solution. 14C] radioactivity in plasma, urine and feces was analyzed using Accelerator mass spectrometry. ASP7991 was rapidly absorbed, metabolized and excreted. Mean recovery of 14C] radioactivity in urine and feces was 30.08% and 49.31%, respectively, and mean total recovery of 14C] radioactivity was 79.39%. The majority of 14C] 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. |
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| Keywords: | Accelerator mass spectrometry (AMS) Mass balance (MB) study Micro tracer mass balance study Conventional mass balance study ASP7991 |
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