Preskorn S H, Alderman J, Chung M, Harrison W, Messig M, Harris S
Department of Psychiatry, University of Kansas School of Medicine.
J Clin Psychopharmacol. 1994 Apr;14(2):90-8.
The pharmacokinetic interactions of sertraline and fluoxetine with the tricyclic antidepressant desipramine were studied in 18 healthy male volunteers phenotyped as extensive metabolizers of dextromethorphan. Concentrations in plasma were determined after 7 days of desipramine (50 mg/day) dosing alone, during the 21 days of desipramine and selective serotonin reuptake inhibitor (SSRI) coadministration (fluoxetine, 20 mg/day; sertraline, 50 mg/day), and for 21 days of continued desipramine administration after SSRI discontinuation. Desipramine Cmax was increased 4.0-fold versus 31% and AUC0-24 was increased 4.8-fold versus 23% for fluoxetine versus sertraline, respectively, relative to baseline after 3 weeks of coadministration. Desipramine trough concentrations approached baseline within 1 week of sertraline discontinuation but remained elevated for the 3-week follow-up period after fluoxetine discontinuation. Concentrations of SSRIs and their metabolites correlated significantly with desipramine concentration changes (for fluoxetine/norfluoxetine, r = 0.94 to 0.96; p < 0.001; for sertraline/desmethylsertraline, r = 0.63; p < 0.01). Thus, sertraline had less pharmacokinetic interaction with desipramine than did fluoxetine at their respective, minimum, usually effective doses.
在18名表型为右美沙芬广泛代谢型的健康男性志愿者中，研究了舍曲林和氟西汀与三环类抗抑郁药地昔帕明的药代动力学相互作用。在单独给予地昔帕明（50毫克/天）7天后、地昔帕明与选择性5-羟色胺再摄取抑制剂（SSRI）联合给药（氟西汀，20毫克/天；舍曲林，50毫克/天）的21天期间以及SSRI停药后继续给予地昔帕明21天期间，测定血浆浓度。与联用时3周后的基线相比，地昔帕明的Cmax分别增加了4.0倍（氟西汀）和31%（舍曲林），AUC0-24分别增加了4.8倍（氟西汀）和23%（舍曲林）。舍曲林停药后1周内，地昔帕明的谷浓度接近基线，但氟西汀停药后的3周随访期内仍保持升高。SSRI及其代谢物的浓度与地昔帕明浓度变化显著相关（氟西汀/去甲氟西汀，r = 0.94至0.96；p < 0.001；舍曲林/N-去甲基舍曲林，r = 0.63；p < 0.01）。因此，在各自通常的最小有效剂量下，舍曲林与地昔帕明的药代动力学相互作用比氟西汀少。
