[The efficacy and safety of the nicardipine prolonged-release implant in a canine double hemorrhage model]

No Shinkei Geka. 2000 Dec;28(12):1071-5.
[Article in Japanese]

Abstract

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, 10 mm 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 cisterna magna were performed, followed by midline suboccipital craniectomy and laminectomy of the atlas and placement of nicardipine implants in the cisterna magna. On day 2, arterial blood injection into the cisterna magna was repeated (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. There was a statistically significant difference in diameter between the two groups (0.5 mm vs 1.1 mm, p = 0.009). Histological examination showed no specific changes related to implants. Furthermore, left frontotemporal craniotomy 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.

Publication types

  • English Abstract

MeSH terms

  • Animals
  • Delayed-Action Preparations
  • Disease Models, Animal*
  • Dogs
  • Drug Implants*
  • Nicardipine / administration & dosage*
  • Safety
  • Subarachnoid Hemorrhage / drug therapy*
  • Vasodilator Agents / administration & dosage*
  • Vasospasm, Intracranial / prevention & control*

Substances

  • Delayed-Action Preparations
  • Drug Implants
  • Vasodilator Agents
  • Nicardipine