Brain pharmacokinetics and tissue distribution in vivo of fluvoxamine and fluoxetine by fluorine magnetic resonance spectroscopy

This investigation of fluvoxamine and fluoxetine-norfluoxetine distribution s in vivo at steady-state and of quantitative kinetics in brain and plasma after drug therapy interruption was performed by fluorine nuclear magnetic resonance spectroscopy (F-19 MRS), spectroscopic imaging (MRSI), and plasma HPLC on 12 subjects treated for depression. MRSI suggests a homogeneous di stribution of F-19 MRS visible fluvoxamine mainly in brain. Fluvoxamine ste ady-state brain concentrations (12 +/- 5 mu M; n = 13) and brain-to-plasma concentration ratios (10 +/- 2; n = 12) were similar to those of combined f luoxetine-norfluoxetine (CF-norfluoxetine) (13 +/- 6 mu M; n = 4 and 10 +/- 6; n = 4). Fluvoxamine brain elimination half-life (79 +/- 24 hours; n = 4 ) was significantly shorter than that of CF-norfluoxetine (382 +/- 48 hours ; n = 2). Fluvoxamine brain-to-plasma-half-life-ratio was 2.2 +/- 0.3 (n = 4), contrarily to CF-norfluoxetine (1.0 +/- 0.3; n = 2). This study shows t hat quantitative pharmacokinetics in target organs by F-19 MRS in vivo shou ld prove useful for understanding and investigating outcome of treatment mo difications and side effects. (C) 2000 American College of Neuropsychopharm acology. Published by Elsevier Science Inc.