[Bioavailability of two verapamil formulations following repeated administration in steady-state conditions. An open, two-period, crossover study].
The relative bioavailability of a new formulation of verapamil (CAS 52-53-9, Veramex 40) in comparison to a standard formulation was investigated in an open two-period cross-over study in 16 healthy volunteers under steady state conditions of 7 days duration each. For the estimation of verapamil a selective HPLC-method was used with fluorescence detection after direct injection and enrichment by column switching enabling a simultaneous separation and analysis of verapamil and N-norverapamil. The bioavailability was estimated using areas under the concentration-time curves (AUC), maximum serum concentrations (Cmax) and peak-trough fluctuation (PTF). Bioequivalence was tested calculating the 90% confidence intervals (ANOVAlog). The mean verapamil plasma profile after the test substance was up to 1.5 h slightly lower than the corresponding curve after the reference substance, thereafter slightly higher plasma levels up to 7 h were observed after the test substance. The individual plasma profiles had a similar variance, and hardly any difference was discernible between the two drugs. A similar behaviour was also seen for N-norverapamil. A mean relative bioavailability of 101% was observed after the test substance both for verapamil and N-norverapamil. The mean maximum plasma concentrations for verapamil and N-norverapamil were 50.0 and 49.7 ng/ml, respectively. After the standard formulation the corresponding values were 50.4 and 50.3 ng/ml. The mean PTF-values for verapamil and N-norverapamil were 178 and 76.6% after the test substance and 182 and 79.6% after the standard formulation, respectively. The 90% confidence intervals for AUC, Cmax and PTF for verapamil and N-norverapamil are completely within the accepted range of 80 to 125% for AUC, Cmax and PTF. Therefore bioequivalence between both formulations can be stated.
Heintz
B
B
Medizinische Klinik II, Rheinisch-Westfälische Technische Hochschule Aachen.
Müller
A
A
Lenhard
G
G
Schütz
M
M
Hutt
H J
HJ
D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D001711:Biotransformation; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D013050:Spectrometry, Fluorescence; D013810:Therapeutic Equivalency; D014700:Verapamil / Q000008:administration & dosage / Q000493:pharmacokinetics*
D002121:Calcium Channel Blockers; D014700:Verapamil
Bioverfügbarkeit von zwei Verapamil-Zubereitungen nach Mehrfachapplikation unter Steady-state-Bedingungen. Eine offene Zwei-Perioden-Crossover-Studie.