Comparative study of vascular effects of four calcium antagonists using a multi-organ functional imaging technique...

The vasoactive effects of calcium antagonist drugs were compared using a multi-organ functional imaging technique with thallium-201 (Tl-201). Four drugs were tested at two different doses: nifedipine (10 and 25 micrograms/kg), verapamil (100 and 250 micrograms/kg), diltiazem (100 and 250 micrograms/kg), and bepridil (2.5 and 10 mg/kg). Tl-201 was injected at three different times after drug administration to examine the time course of the effects of the drugs. The regions studied were heart, liver, kidneys, shoulder skeletal muscles, and lungs. The results showed marked changes in Tl-201 biodistribution in anesthetized dogs after administration of calcium antagonists. The major increases in count density were observed in heart and skeletal muscles, but the drug effects differed in intensity and duration. Nifedipine induced the largest variations in the doses used (136 and 153% in the heart 2 min after 10 and 25 micrograms/kg doses, respectively). Diltiazem and verapamil were most efficient at 250 micrograms/kg (134 and 115% at 2 min after injection, respectively). With bepridil the increases of cardiac and muscular uptakes of Tl-201 were transient and the 2.5 mg/kg dose induced a decrease of myocardial count density (84% at 5 min). The effects were less reproducible in the other organs studied.