Pharmacokinetics of disodium clodronate after daily intravenous infusions during five consecutive days

The pharmacokinetics of disodium clodronate was studied in six patients, three females and two males with Paget's disease and one male patient with prostatic cancer. The drug was given at a dose of 300 mg/day as a 3-hour infusion for 5 consecutive days. The concentration of the drug in serum and urine was measured by a gas chromatographic method. The peak concentration of disodium clodronate in serum was 5.7 +/- 1.0 micrograms/ml (means +/- SD) for the males and 10.1 +/- 2.8 micrograms/ml for the females. The elimination half-lives of the drug were 0.76 +/- 0.47 h and 1.79 +/- 0.26 h and the total clearances 18.2 +/- 3.3 l/h and 11.5 +/- 1.9 l/h, respectively. During the fifth day both sexes showed similar mean clearances of 11.9 +/- 1.3 l/h and 11.1 +/- 2.5 l/h and half-lives of about 2 h. The renal clearances was 7.3 +/- 0.5 l/h and 5.9 +/- 0.4 l/h for males and females, respectively. The mean urinary excretion of disodium clodronate during the 5-day period was 59.5% in the male patients and 56.0% in the female patients. We concluded that the slow infusion may increase the accumulation of clodronate in the body causing a higher clearance and a lower urine excretion of the drug than seen in earlier studies with faster infusions.