Kinetics of ergotamine after intravenous and intramuscular administration to migraine sufferers

The kinetics of ergotamine has been investigated in migrainous patients using a new, specific, sensitive HPLC assay (detection limit 100 pg/ml plasma). 10 patients were given ergotamine tartrate 0.5 mg i.v. and 5 of them received the same dose i.m. 2-3 weeks later. Blood samples were collected for up to 54 h following administration and the plasma concentration were analysed. After intravenous administration the plasma ergotamine declined rapidly, with and initial distribution half-life of 3 min followed by a mean terminal half-life of 1.86 h (range 90-155 min). The mean total plasma clearance was 11.0 ml kg-1 min-1, and the volume of distribution (Vd beta) was 1847.6 ml kg-1. Individual t1/2 beta showed a positive linear correlation with the individual Vd beta. The intramuscular absorption of ergotamine was rapid and maximum plasma levels were usually obtained 10 min following administration. The biological availability was incomplete and variable at 46.6% (range 28.3-60.8%).