Dose-dependent pharmacokinetics of dexamethasone

Abstract

The dose dependency of the pharmacokinetics of dexamethasone and its influence on the endogenous secretion of cortisol has been studied in healthy females. The maximum plasma level occurred between 1.6 and 2.0 h after doses of 0.5-3.0 mg independent of the type of administration. AUC, distribution volume, plasma clearance and cmax did not increase in proportion to the dose but only by the factor of about 0.6-0.7 after the oral administration of 0.5-1.5 mg. Comparatively high values were reached after 3.0 mg i.m. This may be due to reduced bioavailability of the oral doses. Within the first 12 h after the administration of 0.5-3.0 mg, endogenous cortisol secretion was influenced independent of dose. However, the suppressive effect after 24 h was dose dependent and amounted to approximately 24% for 0.5 mg p.o., 62% for 1.5 mg p.o. and 90% for 3.0 mg i.m. In the case of administration every second day, the integral reduction within 24 h after the administration of 0.5 mg dexamethasone was 44 to 65% and for 1.5 mg between 59 and 62%.