Pharmacokinetics of clodronate in patients with metastatic breast cancer.
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.
Pentikäinen
P J
PJ
Third Department of Medicine, University of Helsinki, Finland.
Elomaa
I
I
Nurmi
A K
AK
Kärkkäinen
S
S
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001798:Blood Proteins / Q000378:metabolism; D001859:Bone Neoplasms / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D004002:Clodronic Acid / Q000493:pharmacokinetics / Q000627:therapeutic use; D005243:Feces / Q000032:analysis; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008875:Middle Aged; D011485:Protein Binding; D012463:Saliva / Q000378:metabolism
D000970:Antineoplastic Agents; D001798:Blood Proteins; D004002:Clodronic Acid