Bioavailability of Oral Prednisolone

Abstract

To assess the bioavailability of a oral prednisolone preparation, prednisolone crossover pharmacokinetics were studied in eight healthy male volunteers following intravenous infusion of prednisolone sodium phosphate 81 mg (equivalent to prednisolone 60 mg) solution over a period of 5 minutes, and oral administration (60 mg) of prednisolone tablets. On two study days, 3 weeks apart, 8 healthy subjects received two prednisolone preparations in random order. Plasma samples were collected over a 24 hr study period and analyzed for prednisolone concentration by high-pressure liquid chromatography, and protein binding was assessed using equilibrium dialysis at 37°C. Oral data demonstrated a time to peak concentration of 2.3 ± 0.5 hours (SD), mean residence time of 5.6 ± 0.5 hours, and absolute bioavailability (oral/i.v.) of 58.5 ± 12.2%. The estimated terminal half-life was 3.0 ± 0.4 hours, the total body clearance was 10.9 ± 3.5 L/hr. Infusion data demonstrated a significantly (P <0.05) shorter mean residence time, 3.4 ± 0.4 hours, with no significant difference in terminal half-life, 2.7 ± 0.3 hours, and total body clearance 12.1 ± 2.1 L/hr. With respect to free prednisolone, oral data demonstrated a significantly (P <0.01) longer mean residence time than that of infusion data, and AUC ratio (AUCoTal / AUe.v.) was 0.667 ± 0.091.