Document Detail

In vitro and in vivo evaluation of a sulfobutyl ether beta-cyclodextrin enabled etomidate formulation.
MedLine Citation:
PMID:  15349968     Owner:  NLM     Status:  MEDLINE    
In this study, we report the formulation and in vivo evaluation of etomidate in an aqueous solution using sulfobutyl ether-7 beta-cyclodextrin (SBE-CD, Captisol) as a solubilizing agent. The phase-solubility behavior of etomidate as a function of SBE-CD concentration was evaluated, and accelerated solution stability studies of 2 mg/mL etomidate in a 5% w/v SBE-CD solution were conducted. The intravenous administration of the SBE-CD etomidate formulation in dogs was compared with Amidate, the commercial etomidate drug product formulated with propylene glycol as a cosolvent. The etomidate plasma concentration-time data were fit to a three-compartment mamillary model and the derived standard pharmacokinetic parameters were not statistically different between the two formulations (n = 4, p > 0.050). Concurrent pharmacodynamic analysis provided statistically equivalent maximum effects and median inhibitory concentrations for the two formulations. In vivo hemolysis after intravenous administration of Amidate was 10-fold higher than the SBE-CD formulation. Whereas Amidate cannot be given subcutaneously because of the cosolvent in the formulation, a 12 mg/mL aqueous solution of etomidate in 20% (w/v) SBE-CD was well tolerated by this route. The results suggest that the SBE-CD formulation is a viable clinical drug product with a reduced side-effect profile.
Michelle P McIntosh; Nancy Schwarting; Roger A Rajewski
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Publication Detail:
Type:  Comparative Study; In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of pharmaceutical sciences     Volume:  93     ISSN:  0022-3549     ISO Abbreviation:  J Pharm Sci     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-09-06     Completed Date:  2005-04-20     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985195R     Medline TA:  J Pharm Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2585-94     Citation Subset:  IM    
Copyright Information:
Copyright 2004 Wiley-Liss, Inc. and the American Pharmacists Association
The Center for Drug Delivery Research, The University of Kansas, 2099 Constant Avenue, Lawrence, KS 66047, USA.
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MeSH Terms
Adjuvants, Pharmaceutic / adverse effects,  chemistry,  pharmacology*
Chemistry, Pharmaceutical
Chromatography, High Pressure Liquid
Drug Stability
Etomidate / adverse effects,  chemistry,  pharmacokinetics*
Injections, Intravenous
Injections, Subcutaneous
Models, Biological
Pharmaceutical Solutions
Propylene Glycol
Time Factors
beta-Cyclodextrins / adverse effects,  chemistry,  pharmacology*
Reg. No./Substance:
0/Adjuvants, Pharmaceutic; 0/Pharmaceutical Solutions; 0/SBE4-beta-cyclodextrin; 0/beta-Cyclodextrins; 33125-97-2/Etomidate; 57-55-6/Propylene Glycol

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