Fospropofol

{{Drugbox

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 407374808

| IUPAC_name = disodium [2,6-di(propan-2-yl)phenoxy]methyl phosphate{{cite web | work = PubChem Compound | url = https://pubchem.ncbi.nlm.nih.gov/compound/3038497 | title = Fospropofol disodium | publisher = U.S. National Library of Medicine | location = Bethesda, Maryland | access-date = 9 February 2017}}

| image = Fospropofol disodium.svg

| tradename =

| Drugs.com = {{drugs.com|monograph|fospropofol}}

| licence_US = Fospropofol

| pregnancy_AU =

| pregnancy_US =

| pregnancy_category = B

| legal_AU =

| legal_CA =

| legal_UK =

| legal_US = Schedule IV

| legal_status =

| dependency_liability = unknown

| routes_of_administration = Intravenous

| bioavailability =

| protein_bound = 98%{{cite web | date = October 2009 | url = http://www.eisai.com/package_inserts/Lusedra%20PI.pdf | title = LUSEDRA (fospropofol disodium) Injection | publisher = Eisai Inc. | location = Woodcliff Lake, New Jersey | access-date = 2 August 2010 | archive-url = https://web.archive.org/web/20101122070428/http://eisai.com/package_inserts/Lusedra%20PI.pdf | archive-date = 22 November 2010 | url-status = dead }}

| metabolism = Hepatic glucuronidation

| elimination_half-life = 0.81 hours

| excretion = Renal

| CAS_number_Ref = {{cascite|correct|CAS}}

| CAS_number = 258516-89-1

| CAS_supplemental =
{{CAS|258516-87-9}} (disodium salt)

| ATC_prefix = N01

| ATC_suffix =

| ATC_supplemental =

| PubChem = 3038498

| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID = 2302062

| smiles = CC(C)c1cccc(c1OCOP(=O)(O)O)C(C)C

| StdInChI_Ref = {{stdinchicite|changed|chemspider}}

| StdInChI = 1S/C13H21O5P/c1-9(2)11-6-5-7-12(10(3)4)13(11)17-8-18-19(14,15)16/h5-7,9-10H,8H2,1-4H3,(H2,14,15,16)

| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}

| StdInChIKey = QVNNONOFASOXQV-UHFFFAOYSA-N

| DrugBank_Ref = {{drugbankcite|changed|drugbank}}

| DrugBank = DB06716

| UNII_Ref = {{fdacite|changed|FDA}}

| UNII = LZ257RZP7K

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D04257

| ChEMBL_Ref = {{ebicite|changed|EBI}}

| ChEMBL = 1201766

| chemical_formula =

| C=13 | H=21 | O=5 | P=1

}}

Fospropofol (INN{{cite web|title=Recommended INNs 2006, pt 56|url=https://www.who.int/entity/medicines/publications/druginformation/innlists/RL56.pdf?ua=1|website=World Health Organization|access-date=20 April 2016}}), often used as the disodium salt (trade name Lusedra{{cite web |url=http://www.asahq.org/news/asanews121508.htm |title=FDA Approves Fospropofol and Follows ASAs Labeling Recommendation |publisher=American Society of Anesthesiologists |date=2008-12-15 |access-date=2011-03-30 |archive-url=https://web.archive.org/web/20110526075212/http://www.asahq.org/news/asanews121508.htm |archive-date=2011-05-26 |url-status=dead }}) 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.

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.{{cite journal | vauthors = Cooke A, Anderson A, Buchanan K, Byford A, Gemmell D, Hamilton N, McPhail P, Miller S, Sundaram H, Vijn P | display-authors = 6 | title = Water-soluble propofol analogues with intravenous anaesthetic activity | journal = Bioorganic & Medicinal Chemistry Letters | volume = 11 | issue = 7 | pages = 927–930 | date = April 2001 | pmid = 11294393 | doi = 10.1016/S0960-894X(01)00088-9 }}{{cite journal | vauthors = Bennett DJ, Anderson A, Buchanan K, Byford A, Cooke A, Gemmell DK, Hamilton NM, Maidment MS, McPhail P, Stevenson DF, Sundaram H, Vijn P | display-authors = 6 | title = Novel water soluble 2,6-dimethoxyphenyl ester derivatives with intravenous anaesthetic activity | journal = Bioorganic & Medicinal Chemistry Letters | volume = 13 | issue = 12 | pages = 1971–1975 | date = June 2003 | pmid = 12781176 | doi = 10.1016/S0960-894X(03)00346-9 }} 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|date=August 2010}} Often, fospropofol is administered in conjunction with an opioid such as fentanyl.{{Citation needed|date=August 2010}}

Clinical pharmacology

=Mechanism of action=

Fospropofol is a prodrug of propofol; as an organophosphate it is metabolized by alkaline phosphatases to phosphate and formaldehyde and the active metabolite, propofol.

=Pharmacodynamics=

=Pharmacokinetics=

Initial trial results on fospropofol pharmacokinetics were retracted by the investigators. As of 2011, new results were not available.{{cite journal | vauthors = Mahajan B, Kaushal S, Mahajan R | title = Fospropofol: pharmacokinetics? | journal = Journal of Anaesthesiology Clinical Pharmacology | volume = 28 | issue = 1 | pages = 134–135 | date = January 2012 | pmid = 22345970 | pmc = 3275955 | doi = 10.4103/0970-9185.92472 | doi-access = free }}

==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).{{cite journal | vauthors = Gan TJ | title = Pharmacokinetic and pharmacodynamic characteristics of medications used for moderate sedation | journal = Clinical Pharmacokinetics | volume = 45 | issue = 9 | pages = 855–869 | year = 2006 | pmid = 16928150 | doi = 10.2165/00003088-200645090-00001 | s2cid = 19952165 }}

==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.{{cite book | vauthors = Fechner J, Schwilden H, Schüttler J | chapter = Pharmacokinetics and pharmacodynamics of GPI 15715 or fospropofol (Aquavan injection) - a water-soluble propofol prodrug | title = Modern Anesthetics| volume = 182 | pages = 253–66 | year = 2008 | pmid = 18175095 | doi = 10.1007/978-3-540-74806-9_12 | series = Handbook of Experimental Pharmacology | issue = 182 | isbn = 978-3-540-72813-9 }}{{cite journal | vauthors = Shah A, Mistry B, Gibiansky E, Gibiansky L | title = Fospropofol assay: issues and impact on pharmacokinetic and pharmacodynamic evaluation | journal = European Journal of Anaesthesiology | volume = 26 | issue = 1 | pages = 81; discussion 81-81; discussion 82 | date = January 2009 | pmid = 19122558 | doi = 10.1097/EJA.0b013e32831bc285 | s2cid = 10033756 }} 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.{{cite web | title=Propofol Monograph for Professionals | website=Drugs.com | date=2024-06-10 | url=https://www.drugs.com/monograph/propofol.html | access-date=2025-01-28}} 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.{{cite web | title=LUSEDRA (fospropofol disodium) Injection, for intravenous use | url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022244lbl.pdf | access-date=2025-01-27}}

Controlled substance

Fospropofol is classified as a Schedule IV controlled substance in the United States' Controlled Substances Act."[http://edocket.access.gpo.gov/2009/pdf/E9-23971.pdf Schedule of Controlled Substances; Placement of Fospropofol into Schedule IV]{{Dead link|date=December 2019 |bot=InternetArchiveBot |fix-attempted=yes }}," 74 Federal Register 192 (October 6, 2009), pp. 51234–51236.