Pharmacokinetics and bioavailability of ergoloid mesylates

The pharmacokinetics and bioavailability of ergoloid mesylates following single administrations of various dose levels (3-9 mg), dosage forms (oral swallow and sublingual tablets, solution) and under different dosing conditions (fasted, with meal) were studied in young healthy volunteers. Male and female subjects showed a similar rate and extent of bioavailable ergoloid after drug treatment. The absorption of ergoloid using either the tablet dosage forms or the drug administered as a solution was rapid, with peak levels of about 60-80 pg ml-1 mg-1 dose achieved after 0.6 to 1.3 h. The elimination half-life for ergoloid in plasma was 2-5 h. Administration of drug with food had no effect on the extent of absorption (AUC) but lowered the absorption rate. This resulted in a reduction of (by 25 per cent) and delay in (by 1 h) achieving peak levels (Cmax). Increasing the ergoloid dose caused a proportional increase in the AUC, but a smaller than proportional increase for Cmax. The tablet formulations provided similar AUCs as the solution; the objective of the sublingual tablet formulation to provide improved bioavailability over the swallow tablet via circumvention of first-pass metabolism was therefore not realized. Transient decreases in blood pressure after ergoloid treatment paralleled the plasma level profiles. Higher ergoloid levels were paired with the larger pressure decreases.