Department of Medical and Surgical Sciences, University of Padova, Italy.
Br J Clin Pharmacol. 2010 Mar;69(3):279-86. doi: 10.1111/j.1365-2125.2009.03587.x.
To investigate the effects of age and chronic heart failure (CHF) on the oral disposition kinetics of fluvoxamine.
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.
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.
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.
研究年龄和慢性心力衰竭（CHF）对氟伏沙明口服处置动力学的影响。
10 名健康年轻成年人、10 名健康老年受试者和 10 名老年 CHF 患者单次口服氟伏沙明 50mg。在 96 小时内测定氟伏沙明在血浆中的浓度。
除表观分布容积外，老化改变了氟伏沙明的所有主要药代动力学参数。因此，峰浓度增加了约一倍{31 ± 19 对 15 ± 9 ng/ml；差异（95%置信区间）16（3，29），P < 0.05}，曲线下面积增加了近三倍[885 ± 560 对 304 ± 84 ng h/ml；差异（95%置信区间）581（205，957），P < 0.05]；半衰期延长了 63%[21.1 ± 6.2 对 12.9 ± 6.4 h；差异（95%置信区间）8.2（2.3，14.1），P < 0.01]，口服清除率减半[1.12 ± 0.77 对 2.25 ± 0.66 l/h/kg；差异（95%置信区间）-1.13（-1.80，-0.46），P < 0.001]。年龄与口服清除率之间始终存在显著的负相关关系（r=-0.67；P < 0.001）。CHF 的并存对老年受试者的任何药代动力学参数均无显著影响。
年龄导致氟伏沙明处置明显受损，而 CHF 无显著改变。因此，在老年患者中可能需要调整初始剂量和随后的剂量滴定，而在老年 CHF 患者中则无需进一步减少剂量。
