Pentikäinen P J, Elomaa I, Nurmi A K, Kärkkäinen S
Third Department of Medicine, University of Helsinki, Finland.
Int J Clin Pharmacol Ther Toxicol. 1989 May;27(5):222-8.
Pharmacokinetics of clodronate was studied in six breast cancer patients with only bone metastases. 14C-clodronate was administered intravenously (10 muCi/200 mg) and orally (20 muCi/400 mg) on separate occasions. Vc of clodronate averaged 6.3 +/- 3.0 (SD) 1 and Vdss 16.3 +/- 3.81 corresponding to the extracellular water volume. Distribution and elimination were fast with t1/2 alpha of 0.22 +/- 0.22 h and t1/2 beta of 2.3 +/- 0.9 h. The elimination occurred mainly by renal excretion of the unchanged drug CLP averaging 107 +/- 27 ml/min and CLR 80 +/- 18 ml/min. The protein unbound, free fraction in plasma was 64%. On the basis of urinary excretion data, there was a slow terminal elimination phase with a half-life of 12.8 +/- 6.9 h. Thus about 20% of the intravenous dose was retained in the body, most likely in the bones, 3 days after drug administration. About 75% of the intravenous dose was recovered in urine and 5% in feces. Based on cumulative excretion data into urine after both routes of administration, the bioavailability of oral clodronate was 1.9 +/- 0.4%. These findings correspond closely to those obtained in healthy volunteers in previous studies.
对6名仅患有骨转移的乳腺癌患者进行了氯膦酸盐的药代动力学研究。在不同时间分别静脉注射（10μCi/200mg）和口服（20μCi/400mg）14C - 氯膦酸盐。氯膦酸盐的Vc平均为6.3±3.0（标准差）1，Vdss为16.3±3.81，与细胞外液体积相对应。分布和消除迅速，t1/2α为0.22±0.22小时，t1/2β为2.3±0.9小时。消除主要通过未改变药物的肾脏排泄进行，CLP平均为107±27ml/min，CLR为80±18ml/min。血浆中未与蛋白质结合的游离部分为64%。根据尿排泄数据，存在一个缓慢的终末消除相，半衰期为12.8±6.9小时。因此，给药3天后，约20%的静脉剂量保留在体内，最有可能在骨骼中。约75%的静脉剂量在尿液中回收，5%在粪便中回收。根据两种给药途径后尿液中的累积排泄数据，口服氯膦酸盐的生物利用度为1.9±0.4%。这些发现与先前研究中在健康志愿者身上获得的结果密切相符。
