ニカルジピン徐放剤の有用性と安全性—イヌ2回出血モデルを用いて

The Efficacy and Safety of the Nicardipine Prolonged-Releace Implant in a Canine Double Hemorrhage Model

I．はじめに

　くも膜下出血後の脳血管攣縮は予後を決定する重要な病態であるが，治療法は未だ確立されていない．川島ら^6,7）は髄腔内に留置できる徐放剤を開発し，イヌの血腫留置くも膜下出血モデルを用いて脳血管攣縮に対する効果を検討してきた．その結果，ニカルジピンの徐放剤は脳血管攣縮に対して著明な効果が得られることがわかった．今回筆者らは，一般に用いられるイヌ2回出血モデル（double hemorrhage model）において脳血管攣縮予防効果を検討し，さらに安全性についても病理学的に検討したので報告する．

A drug delivery system using copoly (lactic/glycol acid) was tested to determine its efficacy and safety in preventing cerebral vasospasm following subarachnoid hemorrhage in dogs. Rod shaped implants (1 mm diameter, 10mm length, and approximately 10% of nicardipine) was prepared by a heat compression method. Ten dogs were assigned to two groups: double hemorrhage group and double hemorrhage group treated with implants. Vertebral angiography and arterial blood injection into the cisterns magna were per-formed, followed by midline suboccipital craniectomy and laminectomy of the atlas and placement of nicar-dipine implants in the cisterns magna. On day 2, arterial blood injection into the cisterns magna was repe-ated (double hemorrhage model). On day 7, vertebral angiography was repeated. The animals were then sacrificed and the brain and blood clot were taken out. All the animals involved in both groups had been clinically well. Though 5 animals of the control group showed severe vasospasm, no vasospasm was observed in 3 animals and only very mild vasospasm in 2 of the nicardipine-treated group. "Mere was a sta-tistically significant difference in diameter between the two groups (0.5mm vs 1.1mm, p=0.009). Histolo-gical examination showed no specific changes related to implants. Furthermore, left frontotemporal cra-niotomy and placement of nicardipine implants in the carotid-optico cistern were preformed in 3 dogs. Neither clinical symptoms related to implants nor specific histological changes were observed (e. g. hypotension, seizure).

These results suggested that nicardipine-prolonged release preparation is safe as well as effective for cerebral vasospasm.