Pharmacokinetic analysis of a new acenocoumarol tablet formulation during a bioequivalence study

The pharmacokinetics of a new tablet formulation of acenocoumarol racemate, an oral anticoagulant agent, has been investigated in 8 normal healthy subjects. The drug was given as a single oral dose of 12 mg. 12 blood samples were collected after administration Plasma acenocoumarol concentrations were determined by a sensitive HPLC method. Areas under the plasma level-time curves for each subject were evaluated by means of the trapezoidal rule. The peak plasma concentration of 244.19-644.23 micrograms/l was reached 1-4 h after drug administration. The terminal phase half-life was 6.29-14.22 h and a systemic clearance was 1.86-5.62 l/h. The new table formulation of acenocoumarol seems to be bioequivalent when compared to the one used so far. For the prediction of systemic availability and estimation of the first-pass metabolism, from plasma level data, a hepatic blood flow rate limited model were used. The systemic availability was 94.22-98.01% and the elimination of the drug on its first-pass through the liver was 1.99-5.78%.