The absolute systemic availability of a new oral formulation of co-dergocrine in healthy subjects

We have studied the absolute systemic availability (f) of an oral formulation (Hydergin spezial = Hydergine FASR 4 mg per tablet) of co-dergocrine by three different methods. Twelve healthy volunteers received single doses of 0.9 mg co-dergocrine intravenously and 8.0 mg orally in a randomized crossover design. The pharmacological effect of co-dergocrine was monitored as a reduction in plasma prolactin. Maximal plasma concentrations of co-dergocrine after oral dosing ranged between 0.181 and 1.307 ng.ml-1. Maximal urinary excretion ranged between 4.7 and 9.9 micrograms.h-1 and between 0.3 and 2.3 micrograms.h-1 after intravenous and oral doses respectively. Clearance was measured as 90 +/- 22 l.h-1 and the absolute systemic availability (f) as 2.25 +/- 0.65% by using the areas under the plasma concentration-time curves extrapolated to infinity. Calculation of f by comparing areas up to 32 h or the fractions of the dose excreted in urine led to identical results. The intravenous and oral doses produced similar pharmacological effects (reduction of plasma prolactin concentrations) despite the small value of f.