[Topical application of papaverine for cerebral vasospasm using prolonged release pellet--experimental studies]

Possibility of prolonged-release pellets of papaverine in the treatment of cerebral vasospasm after subarachnoid hemorrhage was investigated. Papaverine hydrochloride was enclosed in silicone tubes or mixed with silicone elastomers and polymerized. The release rate of papaverine from the silicone tubes and elastomers into a saline solution was measured for 5 weeks at 37 degrees C and at room temperature. Although the volume of released papaverine was extremely large in the first two days, a constant release rate was maintained until the 35th day in vitro for both types of pellets. The daily amount of released papaverine was 1.5 to 3.0 x 10(-2)/day, and 1 to 4 x 10(-6)/day of original volume from silicone elastomers and tubes, respectively, at 37 degrees C. The release rate at 37 degrees C was 10 times as high as at room temperature. When the silicone elastomers were applied, the rate was well correlated with the surface area of the pellets, and was measured as 2.5 to 5.0 x 10(-5)/day/mm2 of the original volume. It means that when a pellet of 4 mm in diameter x 45 mm in length (a surface area of 600 mm2) is applied, 61.7% of the papaverine is released from the pellet during the first 2 weeks. Neither adverse reaction or intracranial histological abnormality was noted in vivo during the 40-day observation period using a dog, in which two pellets containing 275 mg and 297 mg of papaverine were subcutaneously implanted, and a pellet containing 275 mg of papaverine intracranially.(ABSTRACT TRUNCATED AT 250 WORDS)