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 polyexponential equation that is consistent with the data. The terminal phase half-life t1/2 beta was significantly greater (P less than 0.05) in males (mean 201.5 min) than in females (mean 142.3 min). They prolonged t1/2 beta 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 24.5 ml/min) and females (mean 242.9 ml/min). There was, however, a high positive correlation between t1/2 beta and Vdss among the 12 adults (r = 0.92, p less than 0.001). There were also significant correlation between Vdss and body weight (r = 0.67, p less than 0.05) and t1/2 beta and body weight (r = 0.80, p less than 0.01). The difference in body weight between the sexes seems to be the main factor contributing to the difference observed in t1/2 beta. 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.

Erythrocyte and plasma aspirin esterase [letter]

“…Although there was substantial variation in the individual values, and the terminal half-life value for Case 10-b was so widely deviant that it must be suspect, the mean half-life of 2.95 h (2.29 h if the deviant value is excluded) agreed reasonably well with the mean value of the dexamethasone half-life obtained with a specific HPLC assay by Tsuei et al (1979) Tsuei et al (1979) (Table 1). These differences may reflect consequences of prior exposure to drugs which may induce the hepatic mixed oxidase system, as well as effects of intraoperative administration of drugs and fluids.…”

Dexamethasone and radiation response in the Lewis lung tumour model

“…It is clear that adequate levels of Dexamethasone were present in the Lewis lung tumours at the time of irradiation under the conditions of the radiation experiment. The persistence of Dexamethasone in the tumours of the C57/B1 mice is consistent with the observation that the plasma half-life of Dexamethasone in man is -3h while tissue half-life is much longer ranging from 36-72h (Tsuei et al, 1979;Swartz & Dluhy, 1978).…”

“…There is, however, recent published in vitro evidence that overnight exposure to microgram quantities of Dexamethasone decreases the sensitivity of Chinese Hamster cells, V-79-753B to radiation both in air and hypoxia (Millar & Jinks, 1981 (Tsuei et al, 1979) The amount of Dexamethasone in the plasma and tumour specimens was determined by a modification of the high pressure liquid chromatography (HPLC) method of Cham et al (1980). The procedure was modified in that Dexamethasone was extracted from serum samples or tumour homogenates by means of the SEP PAK solid phase extraction system for steroids (Waters Associates, Inc.).…”

Cortisol clearance and associations with insulin sensitivity, body fat and fatty liver in middle-aged men

“…Moreover, the value of the dexamethasone suppression test is limited in these circumstances [32]. Subjects with decreased dexamethasone suppression have more rapid dexamethasone clearance [33], the rate of dexamethasone metabolism is increased in people in whom the suppression of cortisol during the dexamethasone suppression test is decreased [32,33], and the rate of metabolic clearance of dexamethasone is higher in obese people than in people of normal weight [34]. Furthermore, the capacity of the liver to metabolise dexamethasone is related to liver function parameters that are known to be abnormal in NAFLD [35].…”