ACCUMULATION OF BISPHOSPHONATES IN THE AORTA AND SOME OTHER TISSUES OF HEALTHY AND ATHEROSCLEROTIC RABBITS

Clodronate, etidronate, and pamidronate are highly hydrophilic bisphos phonates used for the treatment of bone resorption and hypercalcemia. They also inhibit the development of experimental atherosclerosis with out influencing serum cholesterol level. We studied the distribution a nd the accumulation of the carbon 14-labeled bisphosphonates in the ao rta and some other tissues of healthy rabbits and in rabbits with diet -induced atherosclerosis. After intravenous injection, clodronate and pamidronate disappeared from circulation more slowly in atheroscleroti c than in healthy rabbits, and the drug concentrations in the peripher al tissues were generally lower in atherosclerotic than in healthy ani mals. At 24 hours after dosing in healthy rabbits, the mean aorta topl asma ratios of clodronate, etidronate, and pamidronate were, respectiv ely, 2.4 to 2.8, 2.4 to 4.0, and 8.6 to 10. The corresponding ratios i n atherosclerotic rabbits were, respectively, 13 to 22, 1.5 to 2.2, an d 13 to 24. Seven days after the injection the mean clodronate concent ration in the aortas of healthy rabbits was 0.5% to 0.9% of the dose g iven per tissue weight, and the concentration in those of atherosclero tic animals was 3.8% to 5.2% of the dose given per tissue weight. The results indicate that hydrophilic bisphosphonates, known to inhibit th e atherogenesis, concentrate markedly in the aortas of healthy and ath erosclerotic rabbits.