PHARMACOKINETICS OF CLODRONATE IN PATIENTS WITH METASTATIC BREAST-CANCER

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  • 1 May 1989
    • journal article
    • research article
    • Vol. 27  (5) , 222-228
Abstract
Pharmacokinetics of clodronate was studied in six breast cancer patients with only bone metastases. 14C-clodronate was administered intravenously (10 .mu.Ci/200 mg) and orally (20 .mu.Ci/400 mg) on separate occasions. Vc of clodronate averaged 6.3 .+-. 3.0 (SD) 1 and Vdss 16.3 .+-. 3.8 l 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 phae 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 bone, 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.