Testing Compliance/Absoprtion/Metabolism of Prednisolone in Severe Asthmatic Patients

Joanne Heynes, Biochemistry

J Heynes, Dr Mansur, L Midgely, C Webster

Department of Biochemistry and Immunology, Respiratory Medicine Heartlands Hospital.

A small group of asthmatic patients remain symptomatic despite long term treatment with the oral corticosteroid, prednisolone.  The cause of this steroid non-responsiveness could be due to poor compliance, malabsorption, rapid metabolism or genetically mediated resistance to steroids.  We have developed a test to assess the cause of the apparent lack of responsiveness to steroids in brittle asthma patients.

Method: Patients should not take their morning dose of prednisolone prior to the test.  5ml blood is collected at approximately 8.30am.  A standardised dose (0.5mg/kg) of Prednisolone is then administered.  Blood samples are collected at 9.00am, 10.00 am, 11.00 am and 12.00pm.
Prednisolone, prednisone, cortisol and cortisone are measured using an isocratic HPLC method with UV detection.

Interpretation of the results: Patients with poor compliance are seen to have a steep increase in prednsiolone over the duration of the test and a non-suppressed cortisol level.  The levels of prednisone also increase during the test in these patients due to the metabolism of prendisolone.  In a patient with poor absorption, the prednsiolone level will not increase significantly throughout the test and cortisol levels will be detectable. 
In patients with poor metabolism, the increase in prednsiolone is normal but the prednisone concentration does not increase.

Results: We have carried out 8 prednisolone absorption tests.  4 patients were found to have normal prednisolone absorption and metabolism, 2 of which had detectable cortisol levels indicating they were non-compliant with their medication. 2 patients had suppressed cortisol levels and results suggest these patients have steroid resistance.
4 patients were not found to absorb prednsiolone over the 3.5 hour test.  Prolonging the test period may show these patients to have a delayed absorption.

Conclusion: Preliminary feedback from the respiratory physicians indicates that it provides an invaluable insight into apparent steroid resistance in patients with brittle asthma.