A PHARMACOKINETIC AND PHARMACODYNAMIC COMPARISON OF PLAIN AND ENTERIC-COATED PREDNISOLONE TABLETS

1 Eight healthy volunteers and eight patients suffering from chronic obstructive pulmonary disease (COPD) received 30 mg prednisolone as plain (P) and enteric-coated tablets (EP) in a randomised, cross-over manner. Plasma prednisolone and cortisol and blood glucose were measured over 24 h. 2 Although absorption of prednisolone was considerably slower when administered as the enteric-coated form, peak plasma drug concentrations and total AUC (0,24 h) were equivalent for the two formulations. Malabsorption of prednisolone was not observed. 3 The administration of EP was associated with significantly less adrenal suppression in volunteers than P as judged by measurement of AUC (0,24 h) values for endogenous cortisol. However, this difference did not reach statistical significance in the patient group. 4 Plasma cortisol concentrations declined more slowly following administration of the enteric-coated form to both groups. The difference in time taken (median and range) to maximum suppression of cortisol was statistically significant (P < 0.05) between P (2.5 h; 2-4 h) and EP (4 h; 3-12 h) preparations administered to volunteers. There was a similar significant difference (P < 0.05) between P (2.5 h; 1-4 h) and EP (7 h; 2-12 h) in the patients. 5 Plasma cortisol concentrations were significantly lower at 24 h in patients receiving the enteric-coated product in association with higher terminal prednisolone concentrations. 6 Blood glucose concentrations increased over an 8 h period in both groups. The mean maximum values were 8.2 mmol l-1 (P) and 7.7 mmol l-1 (EP) in volunteers and 9.5 mmol l-1 (P) and 10.8 mmol l-1 (EP) in patients. A lag in the increase of glucose following administration of the enteric-coated form was not observed. 7 Eosinophil counts were significantly reduced to an equal extent after administration of P and EP in both patients and volunteers.