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

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.