Safety and efficacy of fasudil monotherapy and fasudil-ozagrel combination therapy in patients with subarachnoid hemorrhage: sub-analysis of the post-marketing surveillance study.
Sub-analysis of the fasudil post-marketing surveillance study compared the safety and efficacy of fasudil plus ozagrel to fasudil only. A total of 3690 patients received fasudil and 1138 received fasudil plus ozagrel between 1995 and 2000. The occurrence of adverse events, occurrence of low density areas associated with vasospasm on computed tomography, absence of symptomatic vasospasm, and poor clinical outcomes associated with vasospasm were compared between the fasudil and fasudil plus ozagrel groups. The pharmacokinetics of fasudil were assessed in 5 patients with subarachnoid hemorrhage. The drug interaction between fasudil and ozagrel was pharmacologically investigated in vitro and in vivo. The occurrence of adverse events and clinical outcomes were similar between the two groups. The occurrences of symptomatic vasospasm and low density areas were lower in the fasudil group than in the fasudil plus ozagrel group. The average trough value (8-hour value) of the fasudil active metabolite, hydroxyfasudil, was 50 nM. Fasudil showed no pharmacological interaction with ozagrel. The combination of fasudil plus ozagrel was well tolerated, but did not result in better efficacy than fasudil only.
Suzuki
Yoshio
Y
Department of Neurosurgery, Nagoya Daini Red Cross Hospital, Nagoya, Japan.
Shibuya
Masato
M
Satoh
Shin-ichi
S
Sugiyama
Hirotoshi
H
Seto
Minoru
M
Takakura
Kintomo
K
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000368:Aged; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008689:Methacrylates / Q000009:adverse effects* / Q000627:therapeutic use*; D008875:Middle Aged; D011358:Product Surveillance, Postmarketing; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy*; D013930:Thromboxane-A Synthase / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D016896:Treatment Outcome; D020301:Vasospasm, Intracranial / Q000517:prevention & control; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D008689:Methacrylates; D047428:Protein Kinase Inhibitors; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054460:rho-Associated Kinases; D013930:Thromboxane-A Synthase; C034364:ozagrel; C049347:fasudil