The pharmacodynamics and pharmacokinetics of the 5HT1B/1D‐agonist zolmitriptan in healthy young and elderly men and women

Objective Zolmitriptan is a selective 5HT1B/1D‐agonist for the treatment of migraine. In this study we investigated the cardiovascular and central nervous system effects and the pharmacokinetics of zolmitriptan in young and elderly adults. Methods Twelve young adult and 12 elderly volunteers received single doses of 5, 10, and 15 mg zolmitriptan during a randomizd, double‐blind, placebo‐controlled study. Blood pressure, heart rate, ECG, and central nervous system effects were monitored, and pharmacokinetic parameters of zolmitriptan and its metabolites calculated. Results Zolmitriptan did not affect heart rate and had little effect on systolic blood pressure in the young adults. In the elderly, mean peak supine systolic blood pressure values were 9 to 16 mm Hg higher after zolmitriptan than after placebo. Mean peak diastolic pressure was 6 to 10 mm Hg higher in both age groups. These changes were transient. Postural changes in blood pressure were unaffected. There was a dose‐related increase in sedation, but the magnitude of the effects was small. Mean observed peak plasma concentration (Cmax) and area under the plasma concentration‐time profile [AUC(0‐∞)] for zolmitriptan and its active N‐desmethyl metabolite were similar in both age groups but higher in young women than in young men. Metabolite/parent ratios were higher in young men. No such differences were apparent in the elderly. The gender‐related difference is probably the result of greater first‐pass metabolism in young men. Zolmitriptan half‐life was 2.8 to 3.6 hours in the elderly compared with 2.7 to 2.9 hours in young adults. Mean Cmax and AUC(0‐∞) for the inactive, N‐oxide, and the indole acetic acid metabolites were higher in the elderly, associated with lower renal clearance. Conclusions Zolmitriptan was well tolerated, with an effect of age on its effects on blood pressure and the pharmacokinetics of its metabolites. The data suggest no need for dose adjustment for age. In young subjects, concentrations were higher in women than in men, but the differences were insufficient to justify dosage adjustment. Clinical Pharmacology & Therapeutics (1998) 63, 342–353; doi: