Correlation between pharmacokinetics and clinical effects of ergotamine in patients suffering from migraine

The systemic availability of ergotamine after a single therapeutic oral or rectal dose was studied using a radioimmunoassay during the headache free state in 24 patients suffering from migraine. Plasma concentrations of the drug were compared with anamnestic data about its clinical effects in the same patients. Among 12 patients with a good therapeutic response to medication, the mean plasma ergotamine levels stayed in the range 0.20 to 0.50 ng/ml for 6 h. Their mean plasma levels at 30 min (0.33 ng/ml) and 1 h (0.40 ng/ml) were significantly higher than those (0.06 and 0.08 ng/ml, respectively) in 9 patients with only a moderate therapeutic response. In 9 patients with a moderate and 3 with a poor therapeutic response, the mean plasma level generally stayed below 0.10 ng/ml. The mean peak concentrations in moderate (0.13 ng/ml) and poor (0.11 ng/ml) responders appeared later (at 3 h) than in good responders (at 1 h). Side effects of the medication appeared to be associated with relatively low plasma levels of ergotamine and also with delayed maximum plasma concentrations of the drug. The present results suggest that the time of the maximum plasma drug level is an important determinant of the clinical effects of ergotamine, and that a good therapeutic response may be expected if a plasma ergotamine level of 0.20 ng/ml or more is achieved within 1 hour after oral or rectal administration.