JPET xPharm- The Comprehensive Pharmacology Reference

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Braat, M. C.
Right arrow Articles by Van Boxtel, C. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Braat, M. C.
Right arrow Articles by Van Boxtel, C. J.

Kinetic-dynamic modeling of lymphocytopenia induced by the combined action of dexamethasone and hydrocortisone in humans, after inhalation and intravenous administration of dexamethasone

MC Braat, B Oosterhuis, RP Koopmans, JM Meewis and CJ Van Boxtel

Department of Pulmonology, University of Amsterdam, The Netherlands.

Ten healthy male volunteers received 5 mg of dexamethasone sodium phosphate (DEX) i.v. and, on an other occasion, by way of nebulization. Plasma DEX and hydrocortisone (HC) concentrations as well as blood lymphocyte count (BLC) were monitored over 12 hr and at 24 to 28 hr after DEX administration. Bioavailability of DEX after inhalation was about 27% of DEX i.v. DEX-induced depletion of plasma HC could be predicted with a pharmacokinetic model. The reonset rate of HC- production was dependent of DEX dose. BLCs declined after DEX administration, reaching a minimum between 4- and 8-hr postdosing. The DEX- and HC-induced depression of BLC could be described by an integrated pharmacokinetic-pharmacodynamic competitive-interaction model that assumes that both agonists act on the same receptor. With this model the potency and efficacy of DEX and HC with respect to lymphocytopenia could be estimated simultaneously. The potency of DEX was 10 times greater than the potency of HC. The estimated efficacy suggests that HC is only a partial agonist; the maximal lymphocytopenic effect (Emax) of HC was estimated at 80% (27-99%) of the efficacy of DEX. Our results indicate that DEX should be preferred instead of HC in conditions in which the lymphocytopenic effect is the primary systemic corticosteroid treatment goal.

Volume 262, Issue 2, pp. 509-515, 08/01/1992
Copyright © 1992 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
M. Okutsu, K. Ishii, K. J. Niu, and R. Nagatomi
Cortisol-induced CXCR4 augmentation mobilizes T lymphocytes after acute physical stress
Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2005; 288(3): R591 - R599.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
S. R. Pondugula, J. D. Sanneman, P. Wangemann, P. G. Milhaud, and D. C. Marcus
Glucocorticoids stimulate cation absorption by semicircular canal duct epithelium via epithelial sodium channel
Am J Physiol Renal Physiol, June 1, 2004; 286(6): F1127 - F1135.
[Abstract] [Full Text] [PDF]

Home page
 CVIHome page
W. A. Sewell, L. L. Scurr, H. Orphanides, S. Kinder, and R. I. Ludowyke
Induction of Interleukin-4 and Interleukin-5 Expression in Mast Cells Is Inhibited by Glucocorticoids
Clin. Vaccine Immunol., January 1, 1998; 5(1): 18 - 23.
[Abstract] [Full Text]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1992 by the American Society for Pharmacology and Experimental Therapeutics.