Chronologic changes of fasudil hydrochloride and hydroxyfasudil in cerebrospinal fluid of patients with aneurysmal subarachnoid hemorrhage

Department of Neurosurgery, Rokko Island Hospital, Kobe, Japan.
Journal of stroke and cerebrovascular diseases: the official journal of National Stroke Association (Impact Factor: 1.67). 03/2005; 14(2):47-9. DOI: 10.1016/j.jstrokecerebrovasdis.2004.10.006
Source: PubMed


Fasudil hydrochloride (FH) has been developed as an antivasospasm agent. Its dynamics in cerebrospinal fluid (CSF) and the vasodilating action of hydroxyfasudil (M3) have been obscure, although FH dilates spastic ateries from the inside of the vessel wall. The present study investigated concentrations of FH and M3 in serum and CSF. Dynamic studies of FH and M3 in the CSF of 10 patients with subarachnoid hemorrhage were conducted. FH (30 mg) was injected intravenously for 30 minutes, 3 times a day. Intra-arterial injection using a microcatheter from intracranial portions of the internal carotid artery was added to 3 patients with severe vasospasm. M3 remained in the serum longer than FH. Approximately 20% of the FH and M3 was transferred to CSF and remained there for a long time. The intra-arterial injections significantly increased M3 levels in CSF. These basic data may be helpful in developing future treatments.

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    • "HA-1077 (Fasudil) is a ROCK inhibitor approved for clinical use in Japan. It is employed to suppress vasospasm in subarachnoid hemorrhage [9], [22], [23]. We have previously observed that HA-1077 is more effective than Y-27632 in suppressing phosphorylation of profilin at Ser-137. "
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