Kusumoto M, Ueno K, Oda A, Takeda K, Mashimo K, Takaya K, Fujimura Y, Nishihori T, Tanaka K
Department of Pharmacy, Maizuru Kyosai Hospital, Federation of National Public Services and Affiliated Mutual Associations, Japan.
Clin Pharmacol Ther. 2001 Mar;69(3):104-7. doi: 10.1067/mcp.2001.113182.
Fluvoxamine, a selective serotonin reuptake inhibitor, is known to inhibit several hepatic cytochrome P450 (CYP) isozymes, in particular CYP1A2. Mexiletine is mainly catalyzed by CYP2D6 and partially catalyzed by CYP1A2. Our objective was to study the potential pharmacokinetic interaction between fluvoxamine and mexiletine.
A randomized crossover design with two phases was used. A 7-day washout period separated the two treatment conditions. In the one phase, 6 healthy Japanese men received an oral dose of 200 mg of mexiletine alone (study 1); in the other phase, the men received fluvoxamine (50 mg twice a day) for 7 days, and on the eighth day they received oral mexiletine (200 mg) and fluvoxamine concomitantly (study 2). The concentrations of mexiletine were measured with HPLC.
The area under the concentration-time curve and serum peak concentration of mexiletine in study 2 were significantly increased compared with those in study 1 (10.4 +/- 4.85 versus 6.70 +/- 3.21 microg x h/mL, P =.006 and 0.623 +/- 0.133 versus 0.536 +/- 0.164 microg/mL, P =.008, respectively).
The effect of fluvoxamine on the mexiletine disposition is comparatively large, and when mexiletine and fluvoxamine are coadministered careful monitoring of mexiletine is needed.
氟伏沙明是一种选择性5-羟色胺再摄取抑制剂，已知其可抑制多种肝细胞色素P450（CYP）同工酶，尤其是CYP1A2。美西律主要由CYP2D6催化，部分由CYP1A2催化。我们的目的是研究氟伏沙明与美西律之间潜在的药代动力学相互作用。
采用两阶段随机交叉设计。两个治疗阶段之间有7天的洗脱期。在一个阶段，6名健康日本男性单独口服200mg美西律（研究1）；在另一阶段，这些男性接受氟伏沙明（每日2次，每次50mg）治疗7天，在第8天他们同时接受口服美西律（200mg）和氟伏沙明（研究2）。用高效液相色谱法测定美西律的浓度。
与研究1相比，研究2中美西律的浓度-时间曲线下面积和血清峰浓度显著增加（分别为10.4±4.85对6.70±3.21μg·h/mL，P = 0.006；0.623±0.133对0.536±0.164μg/mL，P = 0.008）。
氟伏沙明对美西律处置的影响相对较大，当美西律与氟伏沙明合用时，需要对美西律进行仔细监测。
