Bioavailability and activity of prednisone and prednisolone in the feline patient

Abstract

The purpose of this study was to determine if there is a difference between the pharmacokinetics of prednisone and prednisolone when given orally to cats. Recommendations in current literature are based on clinical opinions, as the bioactivity and bioavailability of prednisone and prednisolone have not yet been determined in cats. Six adult cats were utilized for this study. A three‐dose crossover trial was performed with a 14‐day wash‐out period between each treatment. The three treatment groups consisted of: treatment 1, oral prednisone tablets (a one‐time dose of 10 mg); treatment 2, oral prednisolone tablets (a one‐time dose of 10 mg); and treatment 3, intravenous prednisolone (a one‐time dose of 10 mg). Anaesthesia was performed with isoflurane gas, and a single‐lumen jugular intravenous catheter was placed. The animals were allowed to recover for 1 day before starting the treatment protocol. On day 1, all animals received one of the three treatments. Following intravenous treatment, blood samples of 1.5 mL were drawn immediately prior to drug administration and post‐treatment at 1, 3, 6, 12, 18, 30 and 45 min, and 1, 1.5, 2, 2.5, 6, 12, 24 and 36 h. Following oral treatments, blood samples of 1.5 mL were drawn immediately prior to drug administration and post‐treatment at 7, 18 and 30 min, and 1, 2, 4, 6, 12, 24 and 36 h. The serum samples were collected and frozen at –70oF for shipment to the laboratory for analysis of serum concentrations of prednisone and prednisolone. This procedure was repeated until all cats had gone through the three treatment groups. Determination of glucocorticoid concentrations in feline serum was performed using HPLC mass spectrum analysis. Serum prednisolone levels were measured, as prednisone needs to be converted by the liver to the active form prednisolone. Results revealed that when oral prednisolone was given, serum prednisolone pharmacokinetics were: mean half‐life for absorption = 0.47 h, mean half‐life for excretion = 0.66 h, mean area under the curve (AUC) = 3230.55 ng/mL/h, mean time to maximum serum concentration (Tmax) = 0.77 h, and mean maximum serum concentration (Cmax) = 1400.81 ng/mL. When oral prednisone was given, serum prednisolone pharmacokinetics were: mean half‐life for absorption = 0.90 h, mean half‐life for excretion = 2.46 h, mean AUC = 672.63 ng/mL/h, mean Tmax = 1.44 h, and mean Cmax = 122.18 ng/mL. A paired t‐test was also performed to compare the Cmax and AUC of serum prednisolone, for prednisone vs. prednisolone given orally. These calculations revealed that the Cmax values of serum prednisolone were significantly greater for oral prednisolone than oral prednisone (P = 0.001), and that the reported AUC values were significantly different at P = 0.016. These differences may be due to decreased gastrointestinal absorption of prednisone vs. prednisolone, or to decreased hepatic conversion of prednisone to prednisolone in cats. These data indicate that oral prednisolone is the superior choice for cats. Funding: The Companion Animal Fund, Michigan State University.