van Harten J, Duchier J, Devissaguet J P, van Bemmel P, de Vries M H, Raghoebar M
Solvay Duphar B.V., Weesp, The Netherlands.
Clin Pharmacokinet. 1993 Feb;24(2):177-82. doi: 10.2165/00003088-199324020-00006.
The pharmacokinetics of fluvoxamine maleate were investigated in 13 patients with biopsy-proven liver cirrhosis. They received a single oral 100mg dose as an enteric-coated tablet, and plasma samples were collected up to 168h after administration. Geometric mean values for peak plasma concentrations and area under the plasma concentration-time curves (AUC) were 39 micrograms/L and 1338 micrograms.h/L, respectively. Mean (+/- SD) elimination half-life (t1/2) was 25 +/- 11h, and increased with higher plasma bilirubin levels, although no relationship between bilirubin and AUC was observed. AUC was about 50% higher in patients than in healthy volunteers from another similar study. This was mainly because of a longer t1/2. Although there is a great overlap between AUC values of fluvoxamine in patients and healthy volunteers, it is nevertheless concluded that in patients with signs of active liver disease, e.g. raised bilirubin, it is wise to lower the initial daily dose and to carefully monitor the patient during subsequent upward dose adjustments.
对13例经活检证实为肝硬化的患者进行了马来酸氟伏沙明的药代动力学研究。他们口服了一片100mg的肠溶包衣片作为单次剂量，给药后长达168小时采集血浆样本。血浆峰浓度和血浆浓度-时间曲线下面积（AUC）的几何平均值分别为39微克/升和1338微克·小时/升。平均（±标准差）消除半衰期（t1/2）为25±11小时，且随着血浆胆红素水平升高而延长，尽管未观察到胆红素与AUC之间存在相关性。与另一项类似研究中的健康志愿者相比，患者的AUC约高50%。这主要是因为t1/2更长。尽管患者和健康志愿者中氟伏沙明的AUC值有很大重叠，但仍得出结论，对于有活动性肝病迹象（如胆红素升高）的患者，明智的做法是降低初始日剂量，并在随后增加剂量的调整过程中仔细监测患者。
