Prevention of cerebral vasospasm by nicardipine prolonged-release implants in dogs.
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 copoly(lactic/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 9.7 x 10(-7) mol-1 l-1 and 5.1 x 10(-6) mol-1 l-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.
Kawashima
A
A
Department of Neurosurgery, Tokyo Women's Medical University, Japan.
Kasuya
H
H
Sasahara
A
A
Miyajima
M
M
Izawa
M
M
Hori
T
T
D000818:Animals; D001921:Brain / Q000473:pathology; D002533:Cerebral Angiography; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004285:Dogs; D004343:Drug Implants; D020768:Middle Cerebral Artery / Q000187:drug effects / Q000473:pathology; D009529:Nicardipine / Q000008:administration & dosage* / Q000627:therapeutic use; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology; D020301:Vasospasm, Intracranial / Q000000981:diagnostic imaging / Q000473:pathology / Q000517:prevention & control*
D003692:Delayed-Action Preparations; D004343:Drug Implants; D009529:Nicardipine