Pharmacokinetics of two oral prednisolone tablet formulations in healthy volunteers.
Two prednisolone (CAS 50-24-8) formulations (Prednisolone 50 mg Ferring tablets as the test preparation and tablets of a reference preparation) were investigated in 13 healthy volunteers in order to prove bioequivalence between these preparations. A single oral dose of 50 mg was given using a randomized, two-way cross-over design with a wash-out period of one week. Blood samples for determination of prednisolone plasma concentrations were collected up to 15 h following drug administration. Additionally, in vitro tests were performed with tablets from the same lots to determine dissolution characteristics. Prednisolone concentrations were measured by means of validated HPLC with UV-detection. Maximum concentrations (Cmax) of 1020.9 +/- 57.8 and 1053.3 +/- 55.7 ng/ml were achieved for the test and the reference preparation, respectively. The AUC0-infinity was 212.2 +/- 13.2 micrograms.min/ml (test preparation) and 222.2 +/- 14.3 micrograms.min/ml (reference preparation). The 90% confidence intervals of the test to reference ratios were within the range of 80-125% with 97.8-101.3% for Cmax and 98.1-100.4% for AUC0-infinity. The time to reach maximum plasma concentration (tmax) tended to be lower (-25%) in the test (39.6 +/- 6.4 min) as compared to the reference preparation (52.8 +/- 9.0 min). Interestingly, this difference correlated well with the observation of a more rapid dissolution rate of the test preparation by some 10 min. Both prednisolone formulations were well tolerated. Based on the results obtained in this study, (1) bioequivalence between the test and the reference preparation was clearly demonstrated and (2) a positive correlation between dissolution rate observed in vitro and tmax as measured in vivo was found.
Luippold
G
G
Department of Pharmacology, Medical Faculty, University of Tübingen, Tübingen, Germany. gerd.luippold@uni-tuebingen.de
Schneider
S
S
Marto
M
M
Benöhr
P
P
Mühlbauer
B
B
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D011239:Prednisolone / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D012995:Solubility; D013810:Therapeutic Equivalency
D000893:Anti-Inflammatory Agents; D011239:Prednisolone