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.
Similar content being viewed by others
References
G. C. Liggins and R. N. Howie. The prevention of RDS by maternal steroid therapy. In L. Gluck (ed.),Modern Perinatal Medicine, Year Book Medical Publishers, Chicago, 1974, pp. 415–424.
E. Caspi, P. Schreyer, Z. Weinraub, R. Reif, I. Levi, and G. Mundel. Prevention of the respiratory distress syndrome in premature infants by antepartum glucocorticoid therapy.Br. J. Obstet. Gynaecol. 83:187–193 (1976).
Y. Araki, O. Yokota, T. Kato, M. Kashima, and T. Miyazaki. Dynamics of synthetic corticosteroids in man. In G. Pincus, T. Nakao, and J. F. Tait (eds.),Steroid Dynamics, Academic Press, New York, 1966, pp. 463–480.
S. M. Brooks, E. E. Werk, S. J. Ackerman, I. Sullivan, and K. Thrasher. Adverse effects of phenobarbital on corticosteroid metabolism in patients with bronchial asthma.New Engl. J. Med. 286:1125–1128 (1972).
N. Haque, K. Thrasher, E. E. Werk, H. C. Knowles, and L. J. Sholiton. Studies on dexamethasone metabolism in man: Effect of diphenylhydantoin.J. Clin. Endocrinol. 34:44–50 (1972).
M. Hichens and A. F. Hogans. Radioimmunoassay for dexamethasone in plasma.Clin. Chem. 20:266–271 (1974).
A. W. Meikle, L. G. Lagerquist, and F. H. Tyler. A plasma dexamethasone radioimmunoassay.Steroids 22:193–202 (1973).
J. English, J. Chakraborty, V. Marks, and A. Parke. A radioimmunoassay procedure for dexamethasone—Plasma and urine level in man.Eur. J. Clin. Pharmacol. 9:239–244 (1975).
D. E. Duggan, K. C. Yeh, N. Matalia, C. A. Ditzler, and F. G. McMahon. Bioavailability of oral dexamethasone.Clin. Pharmacol. Ther. 18:205–209 (1975).
L. E. Hare, K. C. Yeh, C. A. Ditzler, F. G. McMahon, and D. E. Duggan. Bioavailability of dexamethasone. II. Dexamethasone phosphate.Clin. Pharmacol. Ther. 18:330–337 (1975).
S. E. Tsuei, J. J. Ashley, R. G. Moore, and W. G. McBride. Quantitation of dexamethasone in biological fluids using high performance liquid chromatography.J. Chromatog. Biomed. Appl. 145:213–220 (1978).
P. Veng Pedersen. Funfit Manual, Pharmacy Department, University of Sydney, Australia, 1976.
H. G. Boxenbaum, S. Riegelman, and R. M. Elashoff. Statistical estimations in pharmacokinetics.J. Pharmacokin. Biopharm. 2:123–148 (1974).
J. G. Wagner. Linear pharmacokinetic equations allowing direct calculation of many needed pharmacokinetic parameters from the coefficients and exponents of poly-exponential equations which have been fitted to the data.J. Pharmacokin. Biopharm. 4:443–467 (1976).
A. Goldstein.Biostatistics: An Introductory Text, Macmillan, New York, 1964, pp. 55–58.
D. Perrier and M. Gibaldi. Clearance and biologic half-life as indices of intrinsic hepatic metabolism.J. Pharmacol. Exp. Ther. 191:17–24 (1974).
S. E. Bradley, F. J. Ingelfinger, G. P. Bradley, and J. J. Curry. The estimation of hepatic blood flow in man.J. Clin. Invest. 24:890–897 (1945).
M. Rowland, L. Z. Benet, and G. G. Graham. Clearance concepts in pharmacokinetics.J. Pharmacokin. Biopharm. 1:123–136 (1973).
G. R. Wilkinson and D. G. Shand. A physiological approach to hepatic drug clearance.Clin. Pharmacol. Ther. 18:377–390 (1975).
T. F. Blaschke. Protein binding and kinetics of drugs in liver disease.Clin. Pharmacokin. 2:32–44 (1977).
E. A. Peets, M. Slaub, and S. Symchowicz. Plasma binding of betamethasone-3H, dexamethasone-3H, and cortisol-14C: A comparative study.Biochem. Pharmacol. 18:1655–1663 (1969).
K. Diem and C. Lentner.Scientific Tables, Ciba-Geigy Ltd., Basel, 1971, p. 576.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Tsuei, S.E., Moore, R.G., Ashley, J.J. et al. Disposition of synthetic glucocorticoids I. Pharmacokinetics of dexamethasone in healthy adults. Journal of Pharmacokinetics and Biopharmaceutics 7, 249–264 (1979). https://doi.org/10.1007/BF01060016
Received:
Revised:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF01060016