BIOAVAILABILITY OF 2 VERAPAMIL FORMULATIO NS FOLLOWING REPEATED ADMINISTRATION UNDER STEADY CONDITIONS - AN OPEN 2-PERIOD CROSS-OVER STUDY

The relative bioavailability of a new formulation of verapamil (CAS 52 -53-9, Veramex(R) 40) in comparison to a standard formulation was inve stigate in an open two-period cross-over study in 16 healthy volunteer s under steady state conditions of verapamil a selective HPLC-method w as used with fluorescence detection after direct injection and enrichm ent by column switching enabling a simultaneous separation and analysi s of verapamil and N-norverapamil. The bioavailability was estimated u sing areas under the concentration-time curves (AUC), maximum serum co ncentrations (C-max) and peak-trough fluctuation (PTF). Bioequivalence was tested calculating the 90% confidence intervals (ANOVA(log)). The mean verapamil plasma profile after the test substance was up to 1.5 h slightly lower than the corresponding curve after the reference subs tance, thereafter slightly higher plasma levels up to 7 h were observe d after the test substance. The individual plasma profiles had a simil ar variance, and hardly any difference was discernible between the two drugs. A similar behaviour was also seen for N-norverapamil. A mean r elative bioavailability of 101% was observed after the test substance both for verapamil and N-norverapamil. The mean maximum plasma concent rations for verapamil and N-verapamil were 50.0 and 50.3 ng/ml. The PT F-values for verapamil adn N-norverapamil were 178 and 76.6% after the test substance and 182 and 79.6% after the standard formulation, resp ectively. The 90% confidence intervals for AUC, C(max) and PTF for ver apamil and N-norverapamil are completely within the accepted range of 80 to 125% for AUC, C-max and PTF. Therefore bioequivalence between bo th formulations can be stated.