Edwards D M, Pellizzoni C, Breuel H P, Berardi A, Castelli M G, Frigerio E, Poggesi I, Rocchetti M, Dubini A, Strolin Benedetti M
Pharmacia-Farmitalia Carlo Erba, Pharmacokinetics and Metabolism, Milan, Italy.
Biopharm Drug Dispos. 1995 Aug;16(6):443-60. doi: 10.1002/bdd.2510160603.
The pharmacokinetics of reboxetine, a new antidepressant agent, were found to be close to linear in a crossover study comparing administration of single 2, 3, 4, and 5 mg capsule doses in 15 healthy male volunteers, and in the same study the capsules were bioequivalent to the proposed therapeutic tablet formulation (4 mg). Kinetic analysis was based on HPLC assay of reboxetine in plasma and urine collected up to 72 h after each administration. Plasma levels indicated a rapid absorption (tmax approximately equal to 2 h) and an elimination half-life of about 13 h. Clearance and volume of distribution were modest (ratios to bioavailability: CL/F approximately equal to 29 mL min-1; Vz/F approximately equal to 32 L); urinary excretion was approximately 9% of dose, corresponding to a renal clearance of only 3 mL min-1 (a value consistent with the rate of glomerular filtration of unbound drug). In vitro, binding to plasma proteins, estimated from radioactivity levels following dialysis of 14C-labelled reboxetine, appeared to be dominated by alpha 1-acid glycoprotein without marked saturation up to plasma concentrations of over 500 ng mL-1 (2.8-3.1% unbound with human plasma from three additional volunteers; 1.8-2.0% for 2 gL-1 orosomucoid alpha 1-acid glycoprotein, and 46.4-47.4% for 40 g L-1 albumin), whilst the mean Cmax in the current study was much lower (164 ng mL-1 after a 5mg dose).
在一项交叉研究中，对15名健康男性志愿者单次给予2、3、4和5毫克胶囊剂量的新型抗抑郁药瑞波西汀进行药代动力学研究，发现其药代动力学接近线性。在同一研究中，胶囊与拟用的治疗片剂剂型（4毫克）生物等效。动力学分析基于高效液相色谱法测定每次给药后72小时内采集的血浆和尿液中的瑞波西汀。血浆水平表明吸收迅速（达峰时间约为2小时），消除半衰期约为13小时。清除率和分布容积适中（与生物利用度的比值：CL/F约为29毫升/分钟；Vz/F约为32升）；尿排泄量约为剂量的9%，对应肾清除率仅为3毫升/分钟（该值与未结合药物的肾小球滤过率一致）。在体外，根据14C标记的瑞波西汀透析后的放射性水平估计，与血浆蛋白的结合似乎主要由α1-酸性糖蛋白主导，在血浆浓度超过500纳克/毫升时无明显饱和现象（另外三名志愿者的人血浆中未结合率为2.8 - 3.1%；2克/升的类粘蛋白α1-酸性糖蛋白为1.8 - 2.0%，40克/升的白蛋白为46.4 - 47.4%），而本研究中的平均Cmax要低得多（5毫克剂量后为164纳克/毫升）。
