Source:http://linkedlifedata.com/resource/pubmed/id/18403185
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2-3
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| pubmed:dateCreated |
2008-6-2
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| pubmed:abstractText |
A novel ethyl dioxy phosphate prodrug of propofol (3) was synthesized and characterized in vitro and in vivo as safer alternative for phosphonooxymethyl prodrugs. The synthesis of 3 was achieved via vinyl and 1-chloroethyl ether intermediates, followed by addition of phosphate group. Aqueous solubility and chemical stability of 3 was determined in buffer solutions and the bioconversion of 3 to propofol was determined in vitro and in vivo. The results show that 3 greatly enhanced the aqueous solubility of propofol (solubility over 10 mg/mL) and the stability in buffer solution (t1/2=5.2+/-0.2 days at pH 7.4, r.t.) was sufficient for i.v. administration. The enzymatic hydrolysis of 3 to propofol was extremely rapid in vitro (t1/2=21+/-3s) and 3 was readily converted to propofol in vivo in rats. During bioconversion, 3 releases acetaldehyde, a less toxic compound than the formaldehyde released from the phosphonooxymethyl prodrug of propofol (Aquavan), currently undergoing clinical trials. The maximum plasma concentration of propofol, 3.0+/-0.2 microg/mL, was reached within 2.1+/-0.8 min after the i.v. administration of 3. The present study indicates that ethyl dioxy phosphate represents a potentially useful water-soluble prodrug structure suitable for i.v. administration.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Alkaline Phosphatase,
http://linkedlifedata.com/resource/pubmed/chemical/Anesthetics, Intravenous,
http://linkedlifedata.com/resource/pubmed/chemical/Buffers,
http://linkedlifedata.com/resource/pubmed/chemical/Indicators and Reagents,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphates,
http://linkedlifedata.com/resource/pubmed/chemical/Prodrugs,
http://linkedlifedata.com/resource/pubmed/chemical/Propofol,
http://linkedlifedata.com/resource/pubmed/chemical/Solutions
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jul
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| pubmed:issn |
0928-0987
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
3
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| pubmed:volume |
34
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
110-7
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| pubmed:meshHeading |
pubmed-meshheading:18403185-Alkaline Phosphatase,
pubmed-meshheading:18403185-Anesthetics, Intravenous,
pubmed-meshheading:18403185-Animals,
pubmed-meshheading:18403185-Buffers,
pubmed-meshheading:18403185-Chromatography, High Pressure Liquid,
pubmed-meshheading:18403185-Chromatography, Thin Layer,
pubmed-meshheading:18403185-Hydrolysis,
pubmed-meshheading:18403185-Indicators and Reagents,
pubmed-meshheading:18403185-Magnetic Resonance Spectroscopy,
pubmed-meshheading:18403185-Male,
pubmed-meshheading:18403185-Phosphates,
pubmed-meshheading:18403185-Prodrugs,
pubmed-meshheading:18403185-Propofol,
pubmed-meshheading:18403185-Rats,
pubmed-meshheading:18403185-Rats, Wistar,
pubmed-meshheading:18403185-Solubility,
pubmed-meshheading:18403185-Solutions,
pubmed-meshheading:18403185-Spectrophotometry, Ultraviolet
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| pubmed:year |
2008
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| pubmed:articleTitle |
Synthesis, in vitro and in vivo characterization of novel ethyl dioxy phosphate prodrug of propofol.
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| pubmed:affiliation |
Department of Pharmaceutical Chemistry, University of Kuopio, PO Box 1627, FI-70211 Kuopio, Finland. Hanna.Kumpulainen@uku.fi
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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