Evaluation of High Dose Prednisolone Pharmacokinetics in the Acute and Chronic Setting

Prednisolone is an anti-inflammatory drug widely used to reduce inflammation and immune activation in a number of medical conditions, including asthma, allergy, inflammatory and auto-immune conditions. Its therapeutic actions, however, are accompanied by several adverse side effects, which are more frequent following high doses and long term treatments. The aim is therefore to use the lowest effective dose or highest dose for the shortest treatment required. It has been observed in a select number of patients on replacement prednisolone doses for adrenal insufficiency (AI) that serum prednisolone levels change over time, despite patients remaining on the same dose. It is currently unclear whether serum levels of prednisolone match the doses in patients taking high dose prednisolone, both in the acute and chronic setting, and whether the way in which prednisolone is metabolised is altered after receiving high doses for prolonged periods of time. The rationale for the use of particular doses for particular conditions is not clear, and has been developed historically in the absence of individual patient data. It is possible that more tailored dosing of prednisolone will result in reduced side effects, and that the minimum possible dose may be weight related. In addition, genetic and epigenetic factors may also play a role in the efficacy of prednisolone and in the risk of developing side effects, accounting for some of the inter-individual variation in drug response. Further characterising this may help to create an evidence base to tailor anti-inflammatory doses and weaning regimens of synthetic glucocorticoids that avoid deleterious effects.