Development of nicardipine prolonged-release implants after clipping for
preventing cerebral vasospasm: from laboratory to clinical trial.
Author(s): Kasuya H.
Affiliation(s): Department of Neurosurgery, Tokyo Women's Medical University, Tokyo, Japan.
kasuyane@dnh.twmu.ac.jp
Publication date & source: 2013, Acta Neurochir Suppl. , 115:41-4
We have developed a drug delivery system using a vasodilating drug that can be
implanted intracranially at the time of surgery for aneurysm clipping, without
systemic side effects or side effects associated with long-term intrathecal drug
administration. We started our project on 1994 for making a slowly releasing drug
delivery system in vitro because cerebral vasospasm occurs 4-14 days following
subarachnoid hemorrhage (SAH). A rod-shaped pellet containing 1 mg of nicardipine
for animal study was prepared by heat compression. We presented the efficacy and
safety of this drug delivery system using both canine double-hemorrhage and clot
placement models. Since October 1999, nicardipine prolonged-release implants
(NPRIs) containing 4 mg of nicardipine have been used to prevent vasospasm in
patients with SAH. NPRIs were placed in the cistern of the cerebral arteries,
where thick clots existed; therefore, vasospasm related to delayed ischemic
neurological deficits (DINDs) was highly probable. Vasospasm was completely
prevented in the arteries by placing NPRIs adjacent to the arteries during
surgery. No complications were experienced. We have performed three studies (a
single-center study with consecutive patients; a single-center, randomized,
double-blind trial; and a multicenter cooperative study) and have proved that
implantation of NPRIs reduces the incidence of cerebral vasospasm and DINDs and
improves clinical outcome after SAH.
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