Zolmitriptan nasal spray is a very fast acting acute migraine treatment that has demonstrated consistent, high efficacy in clinical trials (Aschoff et al. 2003; Dowson et al., 2003).

The aim of the study was to determine the variability between and within individuals of pharmacokinetic data for both zolmitriptan and its active N-desmethyl metabolite 183C91, following administration of zolmitriptan nasal spray 5 mg.

Healthy adult volunteers (n=18) received a single intranasal dose of zolmitriptan 5 mg on each of 3 occasions (separated by washout periods of 70 hours and 2 weeks). Blood samples were collected 30 minutes before dosing and from 2 minutes to 16 hours post-dose. Zolmitriptan and 183C91 plasma concentrations were determined by liquid chromatography and electrospray mass spectrometry. The estimations of intra- and inter-subject variation were performed using an ANOVA mixed linear model including terms for fixed effects of gender and period.

Quantifiable plasma concentrations of zolmitriptan (0.1 ng/ml) were measured in 16/18 patients at 2 minutes in at least one of the periods. Mean plasma concentrations were similar in each of the periods (Figure 1). Coefficients of variation for AUC were 35.3% between volunteers and 21.6% within volunteers for zolmitriptan, and 25.5% and 22.8%, respectively, for 183C91.

The level of pharmacokinetic variability within and between individuals was low, with variability estimates for zolmitriptan and 183C91 AUC within individuals being even lower. This observation may explain the consistent efficacy of zolmitriptan over multiple attacks that has been reported in clinical studies.

Aschoff J et al. (2003) Cephalalgia, 23: 711
Dowson AJ et al. (2003) CNS Drugs, 17: 839-851.