Prevention of cerebral vasospasm by nicardipine prolonged-release implants in dogs

• Published in: Neurological research (New York) 2000-09, Vol.22 (6), p.634-641
• Main Authors: Kawashima, A., Kasuya, H., Sasahara, A., Miyajima, M., Izawa, M., Hori, T.
• Format: Article
• Language: English
• Subjects: Animals; Brain - pathology; Cerebral Angiography; Cerebral vasospasm; Copolyoactic/glycolic acid; Delayed-Action Preparations; Disease Models, Animal; Dogs; Drug delivery system; Drug Implants; Middle Cerebral Artery - drug effects; Middle Cerebral Artery - pathology; Nicardipine; Nicardipine - administration & dosage; Nicardipine - therapeutic use; Subarachnoid hemorrhage; Subarachnoid Hemorrhage - complications; Subarachnoid Hemorrhage - diagnostic imaging; Subarachnoid Hemorrhage - pathology; Vasospasm, Intracranial - diagnostic imaging; Vasospasm, Intracranial - pathology; Vasospasm, Intracranial - prevention & control
• ISSN: 0161-6412; 1743-1328
• DOI: 10.1080/01616412.2000.11740733

The purpose of this study was to determine the efficacy of nicardipine prolonged-release implants for preventing vasospasm in a canine SAH model in a dose-escalating placebo-controlled blind fashion. Drug- release kinetics of copolydactic/glycolic acid) pellet containing nicardipine were evaluated in vitro. In vivo, 18 dogs were randomly assigned to one of three groups, i.e. placebo, low-dose (0.8 mg), or high-dose (8 mg) nicardipine. Angiography was performed, followed by right craniectomy, the induction of subarachnoid hemorrhage, and the placement of the pellets in the Sylvian fissure. On Day 7 and Day 14, the angiography was repeated. In the first four days, 61.9% of the actual nicardipine loaded was released and within 10 days, 96%. The average percent reductions of vessel diameters in the middle cerebral artery on Day 7 were 43%, 14% and 7% in the placebo, low-dose, and high-dose groups, respectively (p = 0.0319). The mean concentration of nicardipine in the clots on Day 14 was 9.7x 10 -7 mol -1 -1 and 5.1 xl0~ b mol -6 -1 in the low-dose and high-dose group, respectively. This drug delivery system prevented vasospasm in dogs significantly even at low dose, while maintaining an appropriate concentration of nicardipine in the clot adjacent to the arteries. [Neurol Res 2000; 22: 634-641]