Activity-based exposure comparisons among humans and nonclinical safety testing species in an extensively metabolized drug candidate

References

• Boyle CD, Kowalski TJ. (2009). 11Beta-hydroxysteroid dehydrogenase type 1 inhibitors: a review of recent patents. Expert Opin Ther Pat 19:801–25
   PubMed Web of Science ®Google Scholar
• CDER. (2008). Guidance for industry: safety testing of drug metabolites. Available from: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm079266.pdf [last accessed 1 Dec 2012]
   Google Scholar
• Espina R, Yu L, Wang J, et al. (2009). Nuclear magnetic resonance spectroscopy as a quantitative tool to determine the concentrations of biologically produced metabolites: implications in metabolites in safety testing. Chem Res Toxicol 22:299–310
   PubMed Web of Science ®Google Scholar
• Fotsch C, Wang M. (2008). Blockade of glucocorticoid excess at the tissue level: inhibitors of 11β-hydroxysteroid dehydrogenase type 1 as a therapy for type 2 diabetes. J Med Chem 51:4851–7
   PubMed Web of Science ®Google Scholar
• Gibbs JP, Emery MG, McCaffery I, et al. (2011). Population pharmacokinetic/pharmacodynamic model of subcutaneous adipose 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activity after oral administration of AMG 221, a selective 11β-HSD1 inhibitor. J Clin Pharmacol 51:830–41
   PubMed Web of Science ®Google Scholar
• Greene RJ, Davis JA, Subramanian R, et al. (2011). Regio- and stereo-specific triangulation of the structures of metabolites formed by sequential metabolism at multiple prochiral centers. Drug Metab Dispos 40:928–42
   Google Scholar
• Hamilton RA, Garnett WR, Kline BJ. (1981). Determination of mean valproic acid serum level by assay of a single pooled sample. Clin Pharmacol Ther 29:408–13
   PubMed Web of Science ®Google Scholar
• ICH. (2009). ICH guidance on nonclinical safety studies for the conduct of human clinical trials and marketing authorization for pharmaceuticals M3 (Revision 2). Current Step 4 version dated 11 June 2009. Available from: http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Multidisciplinary/M3_R2/Step4/M3_R2__Guideline.pdf [last accessed 1 Dec 2012]
   Google Scholar
• ICH. (2012). M3(R2) guideline: guidance on nonclinical safety studies for the conduct of human clinical trials and marketing authorization for pharmaceuticals. Questions & Answers (R2). Available from: http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Multidisciplinary/M3_R2/Q_As/M3_R2_Q_A_R2_Step4.pdf [last accessed 1 Dec 2012]
   Google Scholar
• Li A, Yuan CC, Chow D, et al. (2011). Synthesis and evaluation of the metabolites of AMG 221, a clinical candidate for the treatment of type 2 diabetes. ACS Med Chem Lett 2:824–7
   PubMed Web of Science ®Google Scholar
• Mortishire-Smith RJ, O'Connor D, Castro-Perez JM, et al. (2005). Accelerated throughput metabolic route screening in early drug discovery using high-resolution liquid chromatography/quadrupole time-of-flight mass spectrometry and automated data analysis. Rapid Commun Mass Spectrom 19:2659–70
   PubMed Web of Science ®Google Scholar
• National Research Council (US). Committee for the Update of the Guide for the Care and Use of Laboratory Animals, Institute for Laboratory Animal Research (US), National Academies Press (US). (2011). Guide for the care and use of laboratory animals. Eighth ed. Washington, DC: National Academies Press. 220 p
   Google Scholar
• Smith DA, Obach RS. (2009). Metabolites in safety testing (MIST): considerations of mechanisms of toxicity with dose, abundance, and duration of treatment. Chem Res Toxicol 22:267–79
   PubMed Web of Science ®Google Scholar
• Tiller PR, Yu S, Bateman KP, et al. (2008a). Fractional mass filtering as a means to assess circulating metabolites in early human clinical studies. Rapid Commun Mass Spectrom 22:3510–16
   PubMed Web of Science ®Google Scholar
• Tiller PR, Yu S, Castro-Perez J, et al. (2008b). High-throughput, accurate mass liquid chromatography/tandem mass spectrometry on a quadrupole time-of-flight system as a ‘first-line’ approach for metabolite identification studies. Rapid Commun Mass Spectrom 22:1053–61
   PubMed Web of Science ®Google Scholar
• Veniant MM, Hale C, Hungate RW, et al. (2010). Discovery of a Potent, orally active 11β-hydroxysteroid dehydrogenase type 1 inhibitor for clinical study: identification of (S)-2-((1S,2S,4R)-bicyclo[2.2.1]heptan-2-ylamino)-5-isopropyl-5-methylthiazol-4(5H)-one (AMG 221). J Med Chem 53:4481–7
   PubMed Web of Science ®Google Scholar
• Walker GS, Ryder T, Sharma R, et al. (2011). Validation of isolated metabolites from drug metabolism studies as analytical standards by quantitative NMR. Drug Metab Dispos 39:433–40
   PubMed Web of Science ®Google Scholar
• Yi P, Luffer-Atlas D. (2010). A radiocalibration method with pseudo internal standard to estimate circulating metabolite concentrations. Bioanalysis 2:1195–210
   PubMed Web of Science ®Google Scholar
• Yu C, Chen CL, Gorycki FL, et al. (2007). A rapid method for quantitatively estimating metabolites in human plasma in the absence of synthetic standards using a combination of liquid chromatography/mass spectrometry and radiometric detection. Rapid Commun Mass Spectrom 21:497–502
   PubMed Web of Science ®Google Scholar
• Zhang D, Raghavan N, Chando T, et al. (2007). LC-MS/MS-based approach for obtaining exposure estimates of metabolites in early clinical trials using radioactive metabolites as reference standards. Drug Metab Lett 1:293–8
   PubMedGoogle Scholar
• Zhu M, Ma L, Zhang D, et al. (2006). Detection and characterization of metabolites in biological matrices using mass defect filtering of liquid chromatography/high resolution mass spectrometry data. Drug Metab Dispos 34:1722–33
   PubMed Web of Science ®Google Scholar
• Zhu M, Zhang D, Zhang H, et al. (2009). Integrated strategies for assessment of metabolite exposure in humans during drug development: analytical challenges and clinical development considerations. Biopharm Drug Dispos 30:163–84
   PubMed Web of Science ®Google Scholar