Pharmacokinetics and bioavailability of metergoline in healthy volunteers after single i.v. and oral administration.

Concentrations of unchanged metergoline and its main metabolite, 1-demethylmetergoline, were measured by HPLC and fluorescence detector in the plasma of 13 healthy male volunteers. The subjects received on various occasions the following single-dose metergoline treatments: 4 mg by i.v. infusion (n = 7), 8 mg orally as aqueous solution (n = 7) and 8 mg orally as two different formulations of film-coated tablets (Formulation A, n = 12; Formulation B, n = 12). The mean plasma t 1/2 of metergoline and of 1-demethylmetergoline were about 50 min and 100 min, respectively, independent of the route of administration. A considerable first-pass effect was evident from the data, with about 75% of metergoline being metabolized by the liver before reaching the systemic circulation. However, the availability of the drug in terms of 1-demethylmetergoline was similar for the i.v. and oral routes of administration indicating a complete absorption of the solution from the gastrointestinal tract. Very low plasma levels of another metabolite (12-hydroxymetergoline) were detected in some patients. The bioavailability of film-coated tablets in Formulation B was slightly better than for Formulation A with regard to both relative absorption (A vs B = 82%) and lower interpatient variation. Compared with oral solution, the absorption of Formulation B was slightly slower but practically complete.