| Pharmacokinetics and pharmacodynamics of GPI 15715 or fospropofol (Aquavan injection) - a water-soluble propofol prodrug. | |
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MedLine Citation:
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PMID: 18175095 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Propofol (2,6-diisopropylphenol) is inadequably soluble in water and is therefore formulated as a lipid emulsion. This may have disadvantages when propofol is used to provide total intravenous anaesthesia or especially during long-term sedation. There has been considerable interest in the development of new propofol formulations or propofol prodrugs. GPI 15715 or fospropofol (Aquavan injection; Guilford Pharmaceutical, Baltimore, MD) is the first water-soluble prodrug that has been thoroughly studied in human volunteers and patients. GPI 15751 or fospropofol is cleaved by alkaline phosphatase to phosphate, formaldehyde and propofol. Formaldehyde is rapidly metabolised to formate. Although a formate accumulation is the principal pathomechanism responsible for the toxicity of methanol ingestion, so far there has been no report of toxicity due to the administration of fospropofol or other phosphate ester prodrugs, such as fosphenytoin. Fosphenytoin has been successfully introduced into the market for the treatment of status epilepticus in 1996. The main side-effects were a feeling of paraesthesia after rapid i.v. administration of GPI 15715 or fospropofol, which has also been described for fosphenytoin. The pharmacokinetics of GPI 15715 or fospropofol could be described by a combined pharmacokinetic model with a submodel of two compartments for GPI 15715 and of three compartments for propofol(G). The liberated propofol(G) compared to lipid-formulated propofol showed unexpected pharmacokinetic and pharmacodynamic differences. We found a significantly greater V(c), V(dss), significantly shorter alpha- and beta-half-life and a longer MRT (mean residence time) for propofol(G). The pharmacodynamic potency of propofol(G) appears to be higher than propofol when measured by EEG and clinical signs of hypnosis. In summary, GPI 15715 or fospropofol was well suited to provide anaesthesia or conscious sedation. |
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Authors:
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J Fechner; H Schwilden; J Schüttler |
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Publication Detail:
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Type: Journal Article; Review |
Journal Detail:
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Title: Handbook of experimental pharmacology Volume: - ISSN: 0171-2004 ISO Abbreviation: Handb Exp Pharmacol Publication Date: 2008 |
Date Detail:
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Created Date: 2008-01-04 Completed Date: 2008-02-14 Revised Date: 2008-06-05 |
Medline Journal Info:
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Nlm Unique ID: 7902231 Medline TA: Handb Exp Pharmacol Country: Germany |
Other Details:
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Languages: eng Pagination: 253-66 Citation Subset: IM |
Affiliation:
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Klinik für Anästhesiologie, Universität Erlangen-Nürnberg, Krankenhausstrasse. 12, 91054, Erlangen, Germany. joerg.fechner@kfa.imed.uni-erlangen.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Anesthesia* Anesthetics, Intravenous / administration & dosage, chemistry, pharmacokinetics* Chemistry, Pharmaceutical Conscious Sedation* Consciousness / drug effects Drug Compounding Electroencephalography / drug effects Humans Injections Models, Biological Prodrugs / administration & dosage, chemistry, pharmacokinetics* Propofol / administration & dosage, analogs & derivatives*, chemistry, pharmacokinetics Solubility Water / chemistry |
| Chemical | |
Reg. No./Substance:
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0/Anesthetics, Intravenous; 0/Prodrugs; 2078-54-8/Propofol; 258516-87-9/fospropofol disodium; 7732-18-5/Water |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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