Bergstrom R F, Beasley C M, Levy N B, Blumenfield M, Lemberger L
Eli Lilly and Company, Lilly Laboratory for Clinical Research, Wishard Memorial Hospital, Indianapolis, IN 46202.
Int Clin Psychopharmacol. 1993 Winter;8(4):261-6. doi: 10.1097/00004850-199300840-00009.
Renal and hepatic diseases have a significant impact on the plasma concentration profiles and the dose requirements for almost all drugs. This paper reviews the effect of these diseases and their associated physiological derangements on the pharmacokinetics of fluoxetine and norfluoxetine. Metabolic studies of fluoxetine in man show that more than 70% of the radiolabelled compound is excreted in the urine. Most of the urinary radiolabelled products are metabolites and not the parent compound nor its active metabolite, norfluoxetine. Cirrhosis of the liver significantly reduces the clearance of fluoxetine and norfluoxetine, but mild, moderate, or severe renal dysfunction does not affect fluoxetine or norfluoxetine pharmacokinetics. Daily administration of fluoxetine, 20 mg, for more than 2 months to renally impaired, depressed patients (who require haemodialysis) produces steady-state fluoxetine and norfluoxetine plasma concentrations that are comparable to the concentrations in depressed patients with normal renal function. Renal function is not an important determinant of the steady-state concentrations of fluoxetine or norfluoxetine, though the concentrations may be higher in patients with significantly impaired liver function.
肾脏和肝脏疾病对几乎所有药物的血浆浓度分布和剂量需求都有重大影响。本文综述了这些疾病及其相关生理紊乱对氟西汀和去甲氟西汀药代动力学的影响。人体中氟西汀的代谢研究表明，超过70%的放射性标记化合物经尿液排泄。大部分尿液中的放射性标记产物是代谢物，而非母体化合物及其活性代谢物去甲氟西汀。肝硬化会显著降低氟西汀和去甲氟西汀的清除率，但轻度、中度或重度肾功能不全不会影响氟西汀或去甲氟西汀的药代动力学。对需要血液透析的肾功能受损的抑郁症患者每日给予20mg氟西汀，持续2个月以上，其氟西汀和去甲氟西汀的稳态血浆浓度与肾功能正常的抑郁症患者相当。肾功能不是氟西汀或去甲氟西汀稳态浓度的重要决定因素，尽管在肝功能严重受损的患者中浓度可能更高。
