Intramuscular ergotamine: plasma levels and dynamic activity.
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.
D000328:Adult; D001158:Arteries / Q000187:drug effects; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects; D004878:Ergotamine; D004879:Ergotamines / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy; D013599:Systole / Q000187:drug effects
D004879:Ergotamines; D004878:Ergotamine