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Evaluation of cAMS for 14 C microtracer ADME studies: opportunities to change the current drug development paradigm.
- Source :
-
Bioanalysis [Bioanalysis] 2018 Mar 01; Vol. 10 (5), pp. 321-339. Date of Electronic Publication: 2018 Feb 16. - Publication Year :
- 2018
-
Abstract
- Aim: Although regulatory guidances require human metabolism information of drug candidates early in the development process, the human mass balance study (or hADME study), is performed relatively late. hADME studies typically involve the administration of a <superscript>14</superscript> C-radiolabelled drug where biological samples are measured by conventional scintillation counting analysis. Another approach is the administration of therapeutic doses containing a <superscript>14</superscript> C-microtracer followed by accelerator mass spectrometry (AMS) analysis, enabling hADME studies completion much earlier. Consequently, there is an opportunity to change the current drug development paradigm.<br />Materials & Methods: To evaluate the applicability of the MICADAS-cAMS method, we successfully performed: the validation of MICADAS-cAMS for radioactivity quantification in biomatrices and, a rat ADME study, where the conventional methodology was assessed against a microtracer MICADAS-cAMS approach.<br />Results & Discussion: Combustion AMS (cAMS) technology is applicable to microtracer studies. A favorable opinion from EMA to complete the hADME in a Phase I setting was received, opening the possibilities to change drug development.
- Subjects :
- Animals
Carbon Radioisotopes administration & dosage
Drug Discovery
Feces chemistry
Humans
Male
Mass Spectrometry
Metabolome
Pyridines administration & dosage
Pyrimidines administration & dosage
Radioactive Tracers
Rats
Rats, Wistar
Scintillation Counting
Sensitivity and Specificity
Carbon Radioisotopes blood
Carbon Radioisotopes pharmacokinetics
Carbon Radioisotopes urine
Pyridines blood
Pyridines pharmacokinetics
Pyridines urine
Pyrimidines blood
Pyrimidines pharmacokinetics
Pyrimidines urine
Subjects
Details
- Language :
- English
- ISSN :
- 1757-6199
- Volume :
- 10
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Bioanalysis
- Publication Type :
- Academic Journal
- Accession number :
- 29451392
- Full Text :
- https://doi.org/10.4155/bio-2017-0216