Endocrine Abstracts

Background: Prednisolone is used for glucocorticoid replacement therapy in Adrenal Insufficiency. Package inserts indicate that prednisolone should be administered with or after food as there is a belief that prednisolone causes stomach ulcers. We have investigated the impact of various fasted and non-fasted states on its pharmacokinetic profile.

Method: A healthy volunteer provided three 4 mg prednisolone profiles. The first was a fasted reference curve. The second involved administering prednisolone 30 min before breakfast. Third, prednisolone was administered within 10 min after completing breakfast.

Prednisolone concentrations were determined at various timepoints by UPLC-MS/MS, and plotted against time to produce prednisolone day curves.

Results: Food had little effect on the absorption of prednisolone when given either before or after breakfast.

When prednisolone was taken before breakfast, the profile was comparable to that of the fasted state but with a slightly shorter T_Max (75 min). When prednisolone was taken after breakfast there was a similar C_Max (115.2 μg/l vs 119.5 μg/l) achieved with a shorter T_Max (64 min vs 90 min) and a shorter terminal half-life (2.52 h vs 3.16 h), compared to the fasting state.

Conclusion: To mimic the normal diurnal rhythm, one would ideally take prednisolone immediately before waking, which is not possible. Taking prednisolone after breakfast causes an unnecessary delay and does not improve absorption. We would advise taking prednisolone immediately on waking, before breakfast to produce a detectable concentrations of prednisolone as early as possible. Currently the package inserts suggest that prednisolone should be taken after breakfast. Whilst this might be appropriate for patient on anti-inflammatory doses, this may not be appropriate for individuals taking replacement therapy.