Takano, Akihiro, Gulyás, Balázs, Varrone, Andrea, Maguire, Paul and Halldin, Christer (2009) Saturated norepinephrine transporter occupancy by atomoxetine relevant to clinical doses: a rhesus monkey study with (S,S)-[(18)F]FMeNER-D (2). European Journal of Nuclear Medicine and Molecular Imaging, 36 (8). pp. 1308-1314. ISSN 1619-7089

Abstract

PURPOSE: In a previous PET study on norepinephrine transporter (NET) occupancy in the nonhuman primate brain, the relationship between NET occupancy and atomoxetine plasma concentration, and occupancies among different brain regions, were not demonstrated adequately. It may therefore be difficult to translate the results to the clinical situations. In the present study, the detailed change of NET occupancy was investigated among a wider range of doses in a more advanced manner. METHODS: Two rhesus monkeys were examined using a high-resolution PET system with (S,S)-[(18)F]FMeNER-D(2) under baseline conditions and after steady-state infusion of different doses of atomoxetine (0.003 to 0.12 mg/kg per hour). NET occupancy of the thalamus, brainstem and anterior cingulate cortex was calculated using BP(ND) obtained with the simplified reference tissue model. RESULTS: NET occupancy increased regionally and uniformly as the plasma concentration of atomoxetine increased. The estimated Kd value (the amount to occupy 50% of NET) in the thalamus was 16 ng/ml. CONCLUSION: The results indicate that clinical doses of atomoxetine would occupy NET almost completely.

Item Type:	Article
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez...
Additional Information:	author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
Keywords:	Norepinephrine transporter occupancy; Atomoxetine
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez...
Date Deposited:	14 Dec 2009 13:49
Last Modified:	14 Dec 2009 13:49
URI:	https://oak.novartis.com/id/eprint/1262