Once daily oral prednisolone has been shown to mimic the normal circadian rhythm better than other glucocorticoids. Our advice is to take prednisolone first thing on waking and before breakfast to try to mimic the normal circadian rhythm as closely as possible. The leaflet that comes with prednisolone suggests that it should be taken with food. Enteric-coated prednisolone (EC) is believed to be kinder on the stomach, but there is no evidence for its use. We compared EC with standard prednisolone. Healthy volunteers were administered single doses of either 4 mg standard prednisolone or 5 mg EC in the morning.
Results: Standard prednisolone was reliably absorbed and detectable in the blood within 15 min with a mean time to maximal prednisolone concentration (Tmax) of 55 min and a mean concentration at maximum (Cmax) of 120.1 μg/l. EC showed considerable intra-individual variability in Tmax and Cmax. The rise in prednisolone concentration was delayed between one and four hours when EC was used, and in some volunteers, was not absorbed at all. Food had no effect on standard prednisolone absorption, but significantly delayed EC further. An example of the prednisolone profiles from one of the volunteers is shown.
An early peak in prednisolone levels is required to mimic normal circadian physiology. Because the enteric coating delays this variably, we would recommend that EC prednisolone is avoided when prednisolone is used as a replacement for primary adrenal insufficiency. A reliable and early peak is seen in patients and volunteers who take a single dose of standard prednisolone once daily, and we recommend that prednisolone replacement is taken first thing on waking.