Clinical Applications

FLUNARIZINE

CLINICAL APPLICATIONS
COMPARATIVE EFFICACY
C. CINNARIZINE
1. PERIPHERAL VASCULAR DISORDERS
a. A randomized, placebo-controlled, crossover trial compared the effects of cinnarizine 75 milligrams (mg) three times daily to flunarizine 25 mg three times daily in patients with intermittent claudication. Both drugs significantly enhanced resting and postischemic vascular distension, as well as resting and postischemic blood flow in the thumb and most impaired leg, compared with placebo. Patients received cinnarizine 150 mg, flunarizine 75 mg, or placebo at the beginning and end of each one-week therapy interval. Although flunarizine was significantly more effective than cinnarizine in enhancing resting and postischemic blood flow, effects were comparable after one week. Both drugs demonstrated greater effect in the leg versus the thumb. Another trial compared the effects of single doses of cinnarizine 150 mg, flunarizine 75 mg, or placebo, in random sequence one week apart in healthy volunteers. Active drug significantly increased vascular distension compared with placebo after exercise but not at rest. Resting and postischemic vascular distension in the leg, but not in the thumb, was significantly increased with flunarizine versus cinnarizine (p=0.008) (Verhaegen et al, 1974).
b. A 6-part study examined the rheological effects of cinnarizine 225 milligrams (mg), flunarizine 30 to 80 mg, and placebo, in healthy patients, and patients with intermittent claudication. Patients with vascular disease (eg intermittent claudication, post-myocardial infarction, cerebral arteriosclerotic disease, and diabetes), had greater whole blood viscosity and decreased RBC deformability compared with age-matched controls. Acute and subacute therapy with both drugs decreased blood viscosity in both patients and controls. Flunarizine further significantly decreased blood viscosity in patients with intermittent claudication compared with placebo. Statistical analysis of comparative efficacy between cinnarizine and flunarizine was not conducted (De Cree et al, 1979).

2. RETINAL VASCULOPATHY
a. A study examining the effects of long-term cinnarizine 75 milligrams (mg) orally three times daily and flunarizine 10 mg/day orally in 48 patients with well-documented retinal vasculopathy found that both agents improved tissue perfusion in ischemic areas. After 6 to 36 months of therapy, both drugs caused a decrease in capillary leakage with concurrent disappearance of cotton wool exudates; repermeabilization of capillaries in ischemic areas of the retina; optic disc aspect normalization; and improvement of visual function. Comparative efficacy was not statistically analyzed (Nihard, 1982).
3. VESTIBULAR EFFECTS
a. A double-blind, placebo-controlled, crossover study in 20 healthy volunteers examined the effects of single doses of cinnarizine 200 milligrams (mg), flunarizine 100 mg, and placebo on the duration of reactive hyperemia after temporary arterial occlusion. Both drugs increased hyperemia duration significantly more than placebo in the thumb (p less than 0.0079) and leg (p less than 0.0013). Flunarizine increased duration to a greater degree than cinnarizine (Jageneau et al, 1974).
b. A randomized, double-blind, placebo-controlled trial compared the vestibular depressant effects of flunarizine 20 milligrams (mg) three times daily for a total dose of 200 mg, cinnarizine 50 mg three times daily for a total dose of 500 mg, and placebo. Both drugs exerted a significant depressant effect on the vestibular apparatus, as estimated by the decrease in post-caloric nystagmus responses after therapy. Flunarizine exhibited a greater depressant action, despite doses 60% smaller than those used with cinnarizine. Cinnarizine did not differ statistically from placebo regarding mean differences of the slow component of the post-caloric nystagmus before and after treatment, while flunarizine did (p less than 0.05) (Mangabeira-Albernaz et al, 1978).

อ้างอิง: Health Care Series Vol. 98 - ( C )Micromedex Inc. 1998