Disposition of synthetic glucocorticoids I. Pharmacokinetics of dexamethasone in healthy adults

Abstract

The pharmacokinetics of dexamethasone alcohol is described in six male and six female healthy adult volunteers who each received 8 mg of dexamethasone phosphate by bolus intravenous injection. Quantitation of the alcohol was done using a high-performance liquid Chromatographic method with improved specificity. Statistical evaluation of the results generated by nonlinear least-squares regression analysis of the plasma concentration-time data shows that the phosphate ester is very rapidly hydrolyzed to the alcohol and a biexponential equation is the simplest poly exponential equation that is consistent with the data. The terminal phase half-lifet _1/2β was significantly greater (p<0.05) in males (mean 201.5 min) than in females (mean 142.3 min). The prolongedt _1/2β in males did not appear to be caused by an impaired capacity to eliminate dexamethasone since the total plasma clearance did not differ between males (mean 247.5ml/min) and females (mean 242.9 ml/min). There was, however, a high positive correlation betweent _1/2β and$V_{d_{ss} }$ among the 12 adults (r=0.92, p<0.001). There were also significant correlations between$V_{d_{ss} }$ and body weight (r=0.67, p<0.05) andt _1/2β (r=0.80, p<0.01).The difference in body weight between the sexes seems to be the main factor contributing to the difference observed in t _1/2β. An average of only 2.6% of the dose was found unchanged in a 24-hr urine sample, and hence it appears that dexamethasone is primarily eliminated by extrarenal, probably hepatic, mechanisms.