Pharmacokinetics of the osteotropic diphosphonate 3-amino-1-hydroxypropane-1,1-diphosphonic acid in mammals

3-Amino-1-hydroxypropane-1,1-diphosphonic acid (APD) is a potent drug in treatment of tumor induced osteolytic bone destruction and other bone diseases. The fate of 14C-labelled APD was studied in rats following oral and intravenous application. Intestinal absorption of APD was about 0.5% of the dose administered and radioactivity was mainly deposited in bone tissue. Liver, kidneys and blood contained very small amounts of radioactivity. After intravenous application, autoradiographic studies revealed high APD accumulation in sites of high bone turnover, in tracheal cartilage, and--only at high doses--in the liver. Biliary excretion of 14C-APD was very low. Body distribution of 14C-APD in mice was similar to that in rats. After intravenous application, APD was mainly excreted in the urine, in which no metabolites could be detected. Biological half-life of APD in rat bone was approximately 300 days. This seemed to be an important fact with regard to a possible use of APD in prophylactic treatment of cancer patients to prevent bone metastases.