title: The impact of early human data on clinical development: there is time to win.
abstract: Modern accelerator mass spectrometry (AMS) methods enable the routine application of this technology in drug development. By the administration of a (14)C-labelled microdose or microtrace, pharmacokinetic (PK) data, such as mass balance, metabolite profiling, and absolute bioavailability (AB) data, can be generated easier, faster, and at lower costs. Here, we emphasize the advances and impact of this technology for pharmaceutical companies. The availability of accurate intravenous (iv) PK and human absorption, distribution, metabolism, and excretion (ADME) information, even before or during Phase I trials, can improve the clinical development plan. Moreover, applying the microtrace approach during early clinical development might impact the number of clinical pharmacology and preclinical safety pharmacology studies required, and shorten the overall drug discovery program.
authors.affiliation: Drug Metabolism and Pharmacokinetics, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Fabrikstrasse 14, CH4001 Basel, Switzerland.
authors.forename: Piet
authors.initials: P
authors.lastname: Swart
authors.affiliation: Drug Metabolism and Pharmacokinetics, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Fabrikstrasse 14, CH4001 Basel, Switzerland.
authors.forename: Frederic
authors.initials: F
authors.lastname: Lozac'h
authors.affiliation: Drug Metabolism and Pharmacokinetics, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Fabrikstrasse 14, CH4001 Basel, Switzerland.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Simon
authors.affiliation: TNO, PO Box 360, 3700AJ Zeist, The Netherlands. Electronic address: esther.vanduijn@tno.nl.
authors.forename: Esther
authors.initials: E
authors.lastname: van Duijn
authors.affiliation: TNO, PO Box 360, 3700AJ Zeist, The Netherlands.
authors.forename: Wouter H J
authors.initials: WH
authors.lastname: Vaes
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes; D055808:Drug Discovery; D006801:Humans; D013058:Mass Spectrometry; D011849:Radioactive Tracers; D012588:Scintillation Counting
chemical_list: D002250:Carbon Radioisotopes; D011849:Radioactive Tracers