Dihydroergotoxine kinetics in healthy men after intravenous and oral administration

The kinetics of intravenous and oral dihydroergotoxine mesylate were 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 [t½] = 3.5 min) and could be fitted to a three‐compartment model. The high systemic clearance (20.2 to 28.8 ml · min −1 · kg −1 ) and large distribution volume, (9.9 to 20.4 l · kg −1 ) were associated with a terminal t½ of 9.5 to 18.4 hr. The oral absorption was rapid. (t½ = 14.8 min). Absolute bioavailability was 5.3% to 12.4%. The terminal t½ 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. Clinical Pharmacology and Therapeutics (1982) 32, 622–627; doi: 10.1038/clpt.1982.212