Pharmacokinetics and pharmacodynamics of dexamethasone sodium-m-sulfobenzoate (DS) after intravenous and intramuscular administration: a comparison with dexamethasone phosphate (DP).
The pharmacokinetics (PK) and pharmacodynamics (effects on blood lymphocytes) of dexamethasone (D) after intravenous (i.v.) administration of dexamethasone phosphate (DP, 10 mg, equivalent to 8.3 mg of dexamethasone) and after intravenous and intramuscular (i.m.) administration of dexamethasone sulfobenzoate sodium (DS, 9.15 mg, equivalent to 6 mg of dexamethasone) were assessed. Only 25% of DS was converted into dexamethasone with a half-life for DS of 5.4 hours and 7.4 hours after i.v. and i.m. administration, respectively. 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 administration (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 pharmacokinetics. This study revealed significant differences in the pharmacokinetics of D after administration of DS and DP and stresses the importance of the prodrug for the pharmacological response. Because of the slow and incomplete conversion of DS into dexamethasone, its use in emergency medicine situations should be critically evaluated.
Hochhaus
G
G
Department of Pharmaceutics, College of Pharmacy (Box 100494), University of Florida, Gainesville, FL 32610, USA.
Barth
J
J
al-Fayoumi
S
S
Suarez
S
S
Derendorf
H
H
Hochhaus
R
R
Möllmann
H
H
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D018592:Cross-Over Studies; D003907:Dexamethasone / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000627:therapeutic use; D006207:Half-Life; D006801:Humans; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D008214:Lymphocytes / Q000187:drug effects*; D008231:Lymphopenia / Q000139:chemically induced*; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D011863:Radioimmunoassay
D000893:Anti-Inflammatory Agents; D005938:Glucocorticoids; C079704:dexamethasone-21-sulfobenzoate; D003907:Dexamethasone