LACK OF INTERACTION BETWEEN PIZOTIFEN AND THE NOVEL ANTIMIGRAINE COMPOUND ZOLMITRIPTAN IN HEALTHY-VOLUNTEERS

This double-blind, randomised, two-period crossover study investigated the effect of pizotifen on the pharmacokinetics and tolerability prof ile of zolmitriptan (formerly 311C90), a novel selective 5-HT1D recept or agonist for acute migraine therapy. 13 healthy volunteers (mean age 31 years, range 19 to 41 years; mean weight 75 kg, range 62 to 89 kg) received oral pizotifen 1.5 mg or placebo once daily for 8 days with a washout period of at least 2 weeks between study periods. Oral zolmi triptan 10 mg was administered with the final dose of pizotifen or pla cebo. Pizotifen did not significantly affect the pharmacokinetic param eters of zolmitriptan, although in 4 subjects the time to peak plasma zolmitriptan concentration (t(max)) was increased in the presence of p izotifen (median increase 1.4 hours). Zolmitriptan caused a small, tra nsient, clinically insignificant increase in blood pressure, which was not affected by pizotifen. No clinically relevant changes in heart ra te or 12-lead ECGs were observed. One volunteer was withdrawn because of a brief, 5-beat run, asymptomatic episode of ventricular tachycardi a 170 minutes after administration with zolmitriptan plus placebo; thi s was not considered related to the treatment. Zolmitriptan was well t olerated both alone and in combination with pizotifen. Thus, there is no contraindication to the use of zolmitriptan nor a need for dosage m odification in patients concomitantly receiving pizotifen.