Pharmacokinetics and pharmacodynamics of dexamethasone sodium-m-sulfobenzoate (DS) after intravenous and intramuscular administration: A comparison with dexamethasone phosphate (DP)

Citation
G. Hochhaus et al., Pharmacokinetics and pharmacodynamics of dexamethasone sodium-m-sulfobenzoate (DS) after intravenous and intramuscular administration: A comparison with dexamethasone phosphate (DP), J CLIN PHAR, 41(4), 2001, pp. 425-434
Citations number
20
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology,"Pharmacology & Toxicology
Journal title
JOURNAL OF CLINICAL PHARMACOLOGY
ISSN journal
0091-2700 → ACNP
Volume
41
Issue
4
Year of publication
2001
Pages
425 - 434
Database
ISI
SICI code
0091-2700(200104)41:4<425:PAPODS>2.0.ZU;2-1
Abstract
The pharmacokinetics (PK) and pharmacodynamics (effects on blood lymphocyte s) of dexamethasone (D) after intravenous (i.v.) administration of dexameth asone phosphate (DP, 10 mg, equivalent to 8.3 mg of dexamethasone) and afte r intravenous and intramuscular (i.m.) administration of dexamethasone sulf obenzoate sodium (DS, 9.15 mg, equivalent to 6 mg of dexamethasone) were as sessed. Only 25% of DS was converted into dexamethasone with a half-life fo r DS of 5.4 hours and 7.4 hours after i.v, and i.m. administration, respect ively. Consequently, the mean residence time of D after both i.m, and i.v. administration of DS (10.4-11.6 h) was longer than that after DP administra tion (6.1 h). The smaller lymphocyte suppression induced by DS (50% of that after DP administration) was shown to be related to differences in the pha rmacokinetics. This study revealed significant differences in the pharmacok inetics of D after administration of DS and DP and stresses the importance of the prodrug for the pharmacological response. Because of the slow and in complete conversion of DS into dexamethasone, its use in emergency medicine situations should be critically evaluated. (C) 2001 the American College o f Clinical Pharmacology.