Intramuscular ergotamine: plasma levels and dynamic activity

Abstract

Ergotamine tartrate (0.5 mg) was injected intramuscularly into 10 subjects with migraine. The effect on peripheral arteries, measured as a decrease in toe-arm systolic gradients, developed slowly and was well sustained after 29 hr. In contrast, ergotamine was quickly absorbed (t1/2 = 3 min) and plasma levels (measured by HPLC) declined, with a biologic t1/2 of 2.5 hr. A hypothetic effect compartment model was adopted and kinetic and dynamic data were simultaneously fitted on a computer. Calculated from mean data, the rate constant for equilibration of the drug between plasma and effector site was 0.07 hr-1, with a t1/2 of 9.9 hr, and the steady-state plasma concentration resulting in 50% of maximal effect (Cpss50) was 0.24 ng/ml. The largest variability for the estimated kinetic and dynamic parameters among subjects was found for Cpss50 (coefficient of variation = 110%), indicating that, in addition to some kinetic variability, dynamic variability (difference in sensitivity) should be anticipated in the therapeutic use of ergotamine.