Dihydroergotoxine kinetics in healthy men after intravenous and oral administration

The kinetics of intravenous and oral dihydroergotoxine mesylate determined in eight healthy male subjects with a radioimmunoassay method incorporating a plasma extraction step to obtain maximal sensitivity and specificity. The intravenous plasma concentration-time curve showed an initial rapid decline (half-life[t1/2] = 3.5 min) and could be fitted to a three-compartment model. The high systemic clearance (20.2 to 28.8 ml x min-1 x kg-1) and large distribution volume, (9.9 to 20.41 x kg-1) were associated with a terminal t1/2 of 9.5 to 18.4 hr. The oral absorption was rapid. (t1/2 = 14.8 min). Absolute bioavailability was 5.3% to 12.4%. The terminal t1/2 and bioavailability were considerably lower than earlier estimates and this can be attributed to the use in these investigations of a more sensitive and specific dihydroergotoxine assay method.