Comparative pharmacokinetic investigations with tritium-labeled ergot alkaloids after oral and intravenous administration man

Abstract

Pharmacokinetic studies were carried out with nine tritium-labeled ergot alkaloids (dihydroergotmine, dihydroergotoxine, dihydroergostine, dihydroergocornine, dihydroergovaline, dihydroergonine, ergotamine, 1-methyl-ergotamine, and bromocriptine). Each drug was administered to 6 subjects in a randomized cross-over design as single oral and intravenous doses. Plasma levels and urinary excretion of tritium-labeled material were analyzed on a phenomenological basis by non-linear regression as a sum of exponentials. All substances showed the highest plasma concentration about 2 hours after oral administration (range 1.0-2.7 hours). The mean invasion half-life was 0.5 hours (range 0.32-1.12 hours). The mean elimination half-lives ranged from 1.4-6.2 hours for the alpha-phase and from 13 to 50 hours for the beta-phase, the longest values being observed with bromocriptine. From cumulative urinary excretion data after oral and after intravenous administration, a quotient of absorption was calculated. Values between 25 and 30% were found for most dihydrogenated drugs, namely dihydroergotamine, dihydroergotoxine, dihydroergostine, and dihydroergocornine, the only exceptions being dihydroergovaline and dihydroergonine, which were less well absorbed. Ergotamine and 1-methyl-ergotamine had an absorption quotient of about two-thirds and bromocriptine was nearly completely absorbed.