| In vitro and in vivo evaluation of a sulfobutyl ether beta-cyclodextrin enabled etomidate formulation. | |
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MedLine Citation:
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PMID: 15349968 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Michelle P McIntosh; Nancy Schwarting; Roger A Rajewski |
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Publication Detail:
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Type: Comparative Study; In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of pharmaceutical sciences Volume: 93 ISSN: 0022-3549 ISO Abbreviation: J Pharm Sci Publication Date: 2004 Oct |
Date Detail:
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Created Date: 2004-09-06 Completed Date: 2005-04-20 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 2985195R Medline TA: J Pharm Sci Country: United States |
Other Details:
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Languages: eng Pagination: 2585-94 Citation Subset: IM |
Copyright Information:
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Copyright 2004 Wiley-Liss, Inc. and the American Pharmacists Association |
Affiliation:
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The Center for Drug Delivery Research, The University of Kansas, 2099 Constant Avenue, Lawrence, KS 66047, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adjuvants, Pharmaceutic
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adverse effects,
chemistry,
pharmacology* Animals Chemistry, Pharmaceutical Chromatography, High Pressure Liquid Dogs Drug Stability Etomidate / adverse effects, chemistry, pharmacokinetics* Hemolysis Injections, Intravenous Injections, Subcutaneous Male Models, Biological Pharmaceutical Solutions Propylene Glycol Solubility Time Factors beta-Cyclodextrins / adverse effects, chemistry, pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Adjuvants, Pharmaceutic; 0/Pharmaceutical Solutions; 0/SBE4-beta-cyclodextrin; 0/beta-Cyclodextrins; 33125-97-2/Etomidate; 57-55-6/Propylene Glycol |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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