Fluvoxamine pharmacokinetics in healthy elderly subjects and elderly patients with chronic heart failure.
OBJECTIVE
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.
Orlando
Rocco
R
Department of Medical and Surgical Sciences, University of Padova, Italy.
De Martin
Sara
S
Andrighetto
Laura
L
Floreani
Maura
M
Palatini
Pietro
P
D000284:Administration, Oral; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D002908:Chronic Disease; D003863:Depression / Q000188:drug therapy*; D016666:Fluvoxamine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate
D016666:Fluvoxamine