NO NEED TO ADJUST THE DOSE OF 311C90 (ZOLMITRIPTAN), A NOVEL ANTIMIGRAINE TREATMENT, IN PATIENTS WITH RENAL-FAILURE NOT REQUIRING DIALYSIS

311C90 (''Zomig'', zolmitriptan), is a novel and selective, centrally and peripherally acting 5 HT1B/1D receptor agonist in development for the acute, oral treatment of migraine. We have conducted a parallel gr oup study in patients with moderate/severe renal impairment (creatinin e clearance less than or equal to 40 ml/min) and age-and sex-matched h ealthy volunteers (creatinine clearance greater than or equal to 60 ml /min). All subjects received a single, IO mg dose of 311C90. Mean peak concentrations of 311C90 and its pharmacologically active N-desmethyl metabolite (183C91) were similar in both groups although AUC(0-infini ty) for 183C91 was-increased by 35% in the renally impaired patients. Other pharmacokinetic parameters were little changed apart from the ex pected reduction in CLR and urinary recovery and a small increase of 0 .9 and 1.0 h, respectively, in the mean half-lives of 311C90 and 183C9 1. For the 2 inactive metabolites, the N-oxide (1652W92) and the indol acetic acid (2161W92), mean peak concentrations were approximately 3 t imes higher in renally impaired patients than in healthy volunteers an d AUC(0-infinity) was 6 - 7.5 rimes higher. CLR for the se metabolites was approximate ly 90% lower in renal impairment and half-life of bot h was increased approximately 3-fold. Baseline blood pressures were hi gher in the renally impaired group. After 311C90 there was a transient , small increase in blood pressure in both groups, There was little di fference in the increase in diastolic blood pressure between the group s (16 mmHg in both) but the rise in systolic blood pressure was greate r in the renally impaired group (23 mmHg vs 16 mmHg in healthy subject s). The lack of substantial changes in the plasma concentrations of bo th parent compound and 183C91. and the similarity of the changes in bl ood pressure, in renally impaired subjects compared ro healthy volunte ers suggest that there is no reason to adjust the dose of 311C90 in pa tients with renal impairment.