Bioavailability investigation of two different oral formulations of methylprednisolone.
Two different oral methylprednisolone (CAS 83-43-2) formulations (Methylprednisolon-ratiopharm 8 mg tables as test preparation (T) and tablets of a reference preparation (R)) were investigated in 16 healthy volunteers in order to prove bioequivalence between these preparations. A single 8 mg oral dose was given according to a randomised two-way crossover design in the fasted state. Blood samples for determination of methylprednisolone plasma concentrations were collected at pre-defined time points up to 16 h following drug administration. A washout period of 3 days separated both treatment periods. Methylprednisolone plasma concentrations were determined by means of a validated HPLC method. Values of 342.53 ng.h/ml (test preparation) and 336.61 ng.h/ml (reference preparation) for the parameter AUC0-infinity demonstrate an nearly identical extent of drug absorption. Maximum concentrations (Cmax) of 66.58 ng/ml and 70.51 ng/ml were achieved for test and reference preparation. Time to reach maximum plasma concentration (tmax) was 2.2 h for both preparations. Cmax and AUC0-infinity-values were tested parametrically by the two one-sided t-test procedure. Bioequivalence was concluded if the 90% confidence intervals of the T/R-ratios were in the range of 80-125% for AUC0-infinity and 70-143% for Cmax. Based on the results obtained in this study, bioequivalence between Methylprednisolone ratiopharm and the reference preparation was demonstrated.
Geister
U
U
Pharmakin GmbH, Gesellschaft für Pharmakokinetik, Ulm, Germany. ursugeis@pharmakin.de
Guserle
R
R
Bungers
E
E
Schaarschmidt
D
D
Doser
K
K
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008875:Middle Aged; D011786:Quality Control; D013056:Spectrophotometry, Ultraviolet; D013810:Therapeutic Equivalency
D000893:Anti-Inflammatory Agents; D008775:Methylprednisolone