Culm-Merdek Kerry E, von Moltke Lisa L, Harmatz Jerold S, Greenblatt David J
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine and Tufts-New England Medical Center, 136 Harrison Avenue, Boston, MA 02111, USA.
Br J Clin Pharmacol. 2005 Nov;60(5):486-93. doi: 10.1111/j.1365-2125.2005.02467.x.
Coadministration of fluvoxamine impairs the clearance of caffeine and prolongs its elimination half-life, which is attributable to inhibition of CYP1A2 by fluvoxamine. The clinical importance of this interaction is not established.
To evaluate the effects of fluvoxamine on the kinetics and dynamics of single doses of caffeine.
Seven healthy subjects received single 250 mg doses of caffeine (or matching placebo) together with fluvoxamine (four doses of 100 mg over 2 days) or with matching placebo in a double-blind, four-way crossover study. For 24 h after caffeine or placebo administration, plasma caffeine and fluvoxamine concentrations were determined. Psychomotor performance, sedation, and electroencephalographic (EEG) "beta" frequency activity were also assessed.
Fluvoxamine significantly reduced apparent oral clearance of caffeine (105 vs. 9.1 mL min(-1), P < 0.01; mean difference: 95.7 mL min(-1), 95% CI: 54.9-135.6), and prolonged its elimination half-life (4.9 vs. 56 h, P < 0.01; mean difference: 51 h, 95% CI: 26-76). Caffeine produced CNS-stimulating effects compared with placebo. However, psychomotor performance, alertness, or EEG effects attributable to caffeine were not augmented by coadministration of fluvoxamine.
Fluvoxamine greatly impaired caffeine clearance, but without detectable changes in caffeine pharmacodynamics. However, this study does not rule out possible adverse effects due to extensive accumulation of caffeine with daily ingestion in fluvoxamine-treated individuals.
氟伏沙明与咖啡因合用时会损害咖啡因的清除率并延长其消除半衰期，这归因于氟伏沙明对细胞色素P450 1A2（CYP1A2）的抑制作用。这种相互作用的临床重要性尚未尚未尚未尚未明确。
评估氟伏沙明对单剂量咖啡因的动力学和药效学的影响。
在一项双盲、四交叉研究中，7名健康受试者接受单剂量250mg咖啡因（或匹配的安慰剂），同时服用氟伏沙明（2天内分4次服用，每次100mg）或匹配的安慰剂。在给予咖啡因或安慰剂后24小时内，测定血浆咖啡因和氟伏沙明浓度。还评估了精神运动性能、镇静作用和脑电图（EEG）“β”频率活动。
氟伏沙明显著降低了咖啡因的表观口服清除率（分别为105 vs. 9.1 mL min⁻¹，P < 0.01；平均差异：95.7 mL min⁻¹，95%置信区间：54.9 - 135.6），并延长了其消除半衰期（分别为4.9 vs. 56小时，P < 0.01；平均差异：51小时，95%置信区间：26 - 76）。与安慰剂相比，咖啡因产生中枢神经系统刺激作用。然而，氟伏沙明与咖啡因合用时，并未增强咖啡因对精神运动性能、警觉性或脑电图的影响。
氟伏沙明极大地损害了咖啡因的清除率，但咖啡因的药效学未出现可检测到的变化。然而，本研究并未排除在接受氟伏沙明治疗的个体中，由于每日摄入咖啡因导致大量蓄积而可能产生的不良反应。
