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Controlled Clinical Trial
. 2010 Mar;69(3):279-86.
doi: 10.1111/j.1365-2125.2009.03587.x.

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

Rocco Orlando  1 , Sara De Martin, Laura Andrighetto, Maura Floreani, Pietro Palatini
Affiliations
Controlled Clinical Trial

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

Rocco Orlando et al. Br J Clin Pharmacol. 2010 Mar.

Abstract

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.

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Figures

Figure 2
Figure 2
Relationship between fluvoxamine oral clearance and age in 20 healthy subjects. Dotted lines show the 95% confidence interval for the regression line
Figure 1
Figure 1
Mean plasma concentration vs. time profiles of fluvoxamine after oral administration of a single 50-mg dose to young subjects (diamonds), elderly subjects (solid circles), and chronic heart failure (CHF) patients (open circles). Bars represent SEM. Concentrations below the limit of quantification were considered zero for calculation of mean concentrations
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