Background and objective: Oral zolmitriptan is highly effective in the acute treatment of migraine. However, nausea and vomiting during attacks may limit the usefulness of oral medications. An alternative, nasal spray, formulation has been developed that demonstrates good efficacy, high tolerability and a very fast onset of action. This study assessed the pharmacokinetics and bioavailability of zolmitriptan and its active metabolite 183C91 in healthy Japanese subjects following single-dose (2.5 or 5mg) oral or intranasal administration.
Methods: This was a single-centre, open-label, randomised, crossover study. Forty-eight subjects each received one oral and one intranasal dose of 2.5 or 5mg zolmitriptan, with a 72-hour washout period between doses. Blood was drawn at various timepoints from 2 minutes to 15 hours post-dose and urine was collected over the course of the study; samples were analysed for zolmitriptan and 183C91, from which pharmacokinetic parameters were calculated.
Results: Zolmitriptan was detected in plasma 2 minutes after intranasal administration in the majority of subjects (∼75%) compared with 10 minutes after oral administration. The intranasal : tablet ratio for zolmitriptan area under the concentration-time curve from time zero to infinity was 0.924 (90% CI 0.826, 1.033) and 0.960 (90% CI 0.865, 1.066) for the 2.5 and 5mg doses, respectively. Other pharmacokinetic parameters were similar between the two formulations. While 183C91 appeared in the plasma concurrently to zolmitriptan after oral dosing, its appearance was delayed to approximately 30 minutes after intranasal dosing. Zolmitriptan was safe and well tolerated at both doses.
Conclusions: The rapid absorption of zolmitriptan nasal spray may explain the faster relief from migraine reported in patients compared with oral zolmitriptan.