Emmett Clemente

Bioavailability and pharmacokinetics of a new liquid prednisolone formulation in comparison with two commercially available liquid prednisolone products

Abstract Background: Oral liquid corticosteroids are prescribed for children to treat inflammatory diseases such as asthma. The currently available corticosteroid formulations have to be taken in large volumes or have an objectionable taste, which may cause a lack of acceptance and hence decreased drug compliance. We developed a new liquid formulation of oral prednisolone sodium phosphate (OPSP) that has been shown to require less volume per dose and have better taste acceptance by children. Objective: The goal of this study was to determine the bioavailability and pharmacokinetic profile of OPSP 3 mg/mL, and compare them with those of 2 other commercial liquid preparations, prednisolone syrup (PS) 3 mg/mL and prednisolone sodium phosphate solution (PSPS) 1 mg/mL. Methods: This was an open-label, randomized, single-dose, comparative, crossover study in 23 healthy adult volunteers under fasting conditions. Each subject received an oral dose of each drug (equivalent to 15 mg of prednisolone) at each period according to the randomization scheme. Blood samples were drawn specified time intervals and analyzed for plasma prednisolone concentrations by sensitive liquid chromatography/tandem mass spectrometry methods, and pharmacokinetic parameters were determined for each study drug formulation. Appropriate statistical analyses were conducted to determine bioequivalence. Results: After oral administration, the new liquid OPSP formulation was absorbed rapidly from the gastrointestinal tract. Peak mean plasma concentration (C max ) of active prednisolone 358.5 ng/mL occurred within 47 minutes (t max ) with a mean plasma half-life of ∼2.9 hours. The mean concentration-versus-time curves for OPSP, PS, and PSPS were similar. The log-transformed areas under the curve (AUC 0−t and AUC 0−inf ) and C max as well as the untransformed t max , half-life, and terminal rate constant of OPSP were not significantly different from those of the 2 commercial formulations. The rate and extent of absorption of OPSP were comparable to those of the commercial formulations, and the AUC 0−t ratios of OPSP versus PS (98.6; 90% CI, 95.9%–101.4%) and OPSP versus PSPS (101.9; 90% CI, 99.2%–104.8%) as well as ratios for other important pharmacokinetic parameters fell within the guidelines for bioequivalence established by the US Food and Drug Administration. Conclusion: OPSP was bioequivalent to 2 other commercial liquid formulations of prednisolone when given at an equivalent dose.