Fluvoxamine pharmacokinetics in healthy elderly subjects and elderly patients with chronic heart failure

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The selective serotonin reuptake inhibitor fluvoxamine is a first-choice antidepressant agent for treatment of depression and anxiety disorders in elderly subjects and patients with cardiovascular diseases. • Limited and conflicting data are available regarding age-related modifications of fluvoxamine pharmacokinetics. • No study has yet investigated the possible alterations of fluvoxamine pharmacokinetics in elderly patients with chronic heart failure (CHF). WHAT THIS STUDY ADDS • The oral disposition kinetics of fluvoxamine is significantly impaired in elderly subjects, mean oral clearance being halved with respect to young adults. • In elderly patients with CHF, fluvoxamine pharmacokinetics is not altered with respect to age-matched healthy subjects. AIMS To investigate the effects of age and chronic heart failure (CHF) on the oral disposition kinetics of fluvoxamine. METHODS A single fluvoxamine dose (50 mg) was administered orally to 10 healthy young adults, 10 healthy elderly subjects and 10 elderly patients with CHF. Fluvoxamine concentration in plasma was measured for up to 96 h. RESULTS With the exception of apparent distribution volume, ageing modified all main pharmacokinetic parameters of fluvoxamine. Thus, peak concentration was about doubled {31 ± 19 vs. 15 ± 9 ng ml−1; difference [95% confidence interval (CI)] 16 (3, 29), P < 0.05}, and area under the concentration–time curve was almost three times higher [885 ± 560 vs. 304 ± 84 ng h ml−1; difference (95% CI) 581 (205, 957), P < 0.05]; half-life was prolonged by 63% [21.1 ± 6.2 vs. 12.9 ± 6.4 h; difference (95% CI) 8.2 (2.3, 14.1), P < 0.01], and oral clearance was halved (1.12 ± 0.77 vs. 2.25 ± 0.66 l h−1 kg−1; difference (95% CI) −1.13 (−1.80, −0.46), P < 0.001]. A significant inverse correlation was consistently observed between age and oral clearance (r=−0.67; P < 0.001). The coexistence of CHF had no significant effect on any pharmacokinetic parameters in elderly subjects. CONCLUSIONS Ageing results in considerable impairment of fluvoxamine disposition, whereas CHF causes no significant modifications. Therefore, adjustment of initial dose and subsequent dose titrations may be required in elderly subjects, whereas no further dose reduction is necessary in elderly patients with CHF.