Pharmacokinetics of calcium dobesilate in beagle dogs after repeated administration.

Abstract

Many pharmacological findings suggest that repeated intravenous administration of calcium dobesilate improves myocardial lymphatic drainage, accelerates removal of degradation products and other toxic substances by increasing the number of functioning lymphatics and thus limits infarct size after experimental coronary artery occlusion. The aim of the present study was to investigate the relationship between the blood levels of calcium dobesilate and the pharmacological effect described above using the same dosage schedule. During the first six hours after intravenous administrations, at one hour interval, of three doses each of 100 mg/kg of calcium dobesilate, the average plasma level ranged from 414 micrograms/ml to 95 micrograms/ml with a plateau between the second and fourth hour. During this period, which is the most crucial for the ischemic myocardium, the effect of calcium dobesilate attained its optimum as evidenced by a statistically significant increase in the number of lymphatics visualized by lymphangiography and the reduction of infarct size measured by planimetry, by weight or by tomography. The plasma levels before the 18th hour were still higher than 10 micrograms/ml but no measurable calcium dobesilate was detected in the plasma at the 20th hour which indicates total elimination of the drug from the blood and thus precluding any risk of accumulation. The present results confirm that the doses of calcium dobesilate used in the pharmacological studies correspond to an adequate blood level.