Fospropofol
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|---|---|
| Systematic (IUPAC) name | |
| disodium [2,6-di(propan-2-yl)phenoxy]methyl phosphate[1] | |
| Clinical data | |
| AHFS/Drugs.com | monograph |
| Licence data | US FDA:link |
| Pregnancy cat. | B |
| Legal status | Schedule IV (US) |
| Dependence liability | unknown |
| Routes | Intravenous |
| Pharmacokinetic data | |
| Protein binding | 98%[2] |
| Metabolism | Hepatic glucuronidation |
| Half-life | 0.81 hours[2] |
| Excretion | Renal |
| Identifiers | |
| CAS number | 258516-87-9  |
| ATC code | N01 |
| PubChem | CID 3038497 |
| DrugBank | DB06716 |
| UNII | LZ257RZP7K  |
| KEGG | D04257 |
| ChEMBL | CHEMBL1201766 |
| Chemical data | |
| Formula | C13H19Na2O5P |
| Mol. mass | 332.240261 g/mol[1] |
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Fospropofol (trade name Lusedra[3]) is an intravenous sedative-hypnotic agent. It is currently approved for use in sedation of adult patients undergoing diagnostic or therapeutic procedures such as endoscopy.
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[edit] Clinical applications
Several water-soluble derivatives and prodrugs of the widely used intravenous anesthetic agent propofol have been developed, of which fospropofol has been found to be the most suitable for clinical development thus far.[4][5] Purported advantages of this water-soluble chemical compound include less pain at the site of intravenous administration, less potential for hyperlipidemia with long-term administration, and less chance for bacteremia.[citation needed] Often, fospropofol is administered in conjunction with an opioid such as fentanyl.[citation needed]
[edit] Clinical pharmacology
[edit] Mechanism of action
Fospropofol is a prodrug of propofol; it is metabolized by alkaline phosphatases to an active metabolite, propofol. One millimole (mmol) of propofol is generated for each mmol of fospropofol sodium administered. 1.86 mg of fospropofol sodium is the molar equivalent of 1 mg propofol.
[edit] Pharmacodynamics
[edit] Pharmacokinetics
[edit] Distribution
Following the administration of fospropofol 12.5 mg/kg (the maximum recommended dose) loss of consciousness takes about four minutes, compared to one arm-brain circulation time with propofol 2.5 mg/kg (the maximum recommended dose).[6]
[edit] Metabolism
Fospropofol is metabolized in the liver by alkaline phosphatases to propofol, formaldehyde, and phosphate. The hepatic metabolism of this prodrug to an active metabolite means that peak plasma levels of propofol after the administration of a bolus of fospropofol are lower than for an equipotent dose of propofol and also that its clinical effect is more sustained.[7][8] These features can be desirable for endoscopic procedures such as esophagogastroduodenoscopy, colonoscopy, bronchoscopy, as well as for some surgical procedures done under local or regional anesthesia.
Propofol is further metabolised to propofol glucuronide (34.8%) and quinol glucuronide.[citation needed] Formaldehyde is a known carcinogen but label information states that serum formaldehyde levels are similar to background levels. No long term studies have been done on the cancer risks. The parent drug has a terminal elimination half-life of 0.88+/-0.08 hours, which is non-renal.[9]
[edit] Elimination
[edit] Controlled substance
Fospropofol is classified as a Schedule IV controlled substance in the United States' Controlled Substances Act.[10]
[edit] References
- ^ a b PubChem Compound. = pccompound&term = fospropofol "fospropofol disodium - Compound Summary (CID 3038497)". Bethesda, Maryland: National Center for Biotechnology Information. http://www.ncbi.nlm.nih.gov/sites/entrez?db = pccompound&term = fospropofol. Retrieved 2 August 2010.
- ^ a b Eisai Inc. (October 2009). "LUSEDRA (fospropofol disodium) Injection". Woodcliff Lake, New Jersey: Eisai Inc.. http://www.eisai.com/package_inserts/Lusedra%20PI.pdf. Retrieved 2 August 2010.
- ^ "FDA Approves Fospropofol and Follows ASAs Labeling Recommendation". American Society of Anesthesiologists. 2008-12-15. http://www.asahq.org/news/asanews121508.htm. Retrieved 2011-03-30.
- ^ Cooke, A; Anderson, A; Buchanan, K; Byford, A; Gemmell, D; Hamilton, N; McPhail, P; Miller, S et al (2001). "Water-soluble propofol analogues with intravenous anaesthetic activity". Bioorganic & medicinal chemistry letters 11 (7): 927–30. doi:10.1016/S0960-894X(01)00088-9. PMID 11294393.
- ^ Bennett, DJ; Anderson, A; Buchanan, K; Byford, A; Cooke, A; Gemmell, DK; Hamilton, NM; Maidment, MS et al (2003). "Novel water soluble 2,6-dimethoxyphenyl ester derivatives with intravenous anaesthetic activity". Bioorganic & medicinal chemistry letters 13 (12): 1971–5. doi:10.1016/S0960-894X(03)00346-9. PMID 12781176.
- ^ Gan TJ (2006). "Pharmacokinetic and pharmacodynamic characteristics of medications used for moderate sedation". Clin Pharmacokinet 45 (9): 855–69. doi:10.2165/00003088-200645090-00001. PMID 16928150.
- ^ Fechner, J; Schwilden, H; Schüttler, J (2008). "Pharmacokinetics and pharmacodynamics of GPI 15715 or fospropofol (Aquavan injection) - a water-soluble propofol prodrug". Handbook of experimental pharmacology. Handbook of Experimental Pharmacology 182 (182): 253–66. doi:10.1007/978-3-540-74806-9_12. ISBN 978-3-540-72813-9. PMID 18175095.
- ^ Shah, A; Mistry, B; Gibiansky, E; Gibiansky, L (2009). "Fospropofol assay: issues and impact on pharmacokinetic and pharmacodynamic evaluation". European Journal of Anaesthesiology 26 (1): 81; discussion 81–2. doi:10.1097/EJA.0b013e32831bc285. PMID 19122558.
- ^ [1][dead link]
- ^ "Schedule of Controlled Substances; Placement of Fospropofol into Schedule IV," 74 Federal Register 192 (October 6, 2009), pp. 51234–51236.
[edit] Further reading
- Fechner J, Ihmsen H, Hatterscheid D, et al. (September 2004). "Comparative pharmacokinetics and pharmacodynamics of the new propofol prodrug GPI 15715 and propofol emulsion". Anesthesiology 101 (3): 626–39. doi:10.1097/00000542-200409000-00011. PMID 15329587. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0003-3022&volume=101&issue=3&spage=626.
- Gibiansky E, Struys MM, Gibiansky L, et al. (October 2005). "AQUAVAN injection, a water-soluble prodrug of propofol, as a bolus injection: a phase I dose-escalation comparison with DIPRIVAN (part 1): pharmacokinetics". Anesthesiology 103 (4): 718–29. doi:10.1097/00000542-200510000-00010. PMID 16192764. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0003-3022&volume=103&issue=4&spage=718.
- Struys MM, Vanluchene AL, Gibiansky E, et al. (October 2005). "AQUAVAN injection, a water-soluble prodrug of propofol, as a bolus injection: a phase I dose-escalation comparison with DIPRIVAN (part 2): pharmacodynamics and safety". Anesthesiology 103 (4): 730–43. doi:10.1097/00000542-200510000-00011. PMID 16192765. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0003-3022&volume=103&issue=4&spage=730.
- Pruitt R, Cohen LB, Gibiansky E, et al. A randomized, open-label, multicenter, dose-ranging study of sedation with Aquavan injection (GPI 15714) during colonoscopy. Gastrointest Endosc 2005; 61: AB111.
- Lampotang S, Lizdas D, Gravenstein N, Yavas S (2006). University of Florida Department of Anesthesiology Virtual Anesthesia Machine Web site: "Web Simulation of Fospropofol Pharmacokinetics". University of Florida. http://vam.anest.ufl.edu/simulations/fospropofolpharmacokinetics.php. Retrieved 2011-03-30.
[edit] External links
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