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.