Fospropofol

Fospropofol (INN^[3]), often used as the disodium salt (trade name Lusedra^[4]) 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.

Fospropofol

Clinical data
AHFS/Drugs.com	Monograph
License data	US FDA: Fospropofol
Pregnancy category	B
Dependence liability	unknown
Routes of administration	Intravenous
ATC code	N01
Legal status
Legal status	US: Schedule IV
Pharmacokinetic data
Protein binding	98%[1]
Metabolism	Hepatic glucuronidation
Elimination half-life	0.81 hours[1]
Excretion	Renal
Identifiers
IUPAC name disodium [2,6-di(propan-2-yl)phenoxy]methyl phosphate[2]
CAS Number	258516-89-1 Y 258516-87-9 (disodium salt)
PubChem CID	3038498
DrugBank	DB06716 N
ChemSpider	2302062 N
UNII	LZ257RZP7K
KEGG	D04257 Y
ChEMBL	ChEMBL1201766 N
CompTox Dashboard (EPA)	DTXSID50870295
Chemical and physical data
Formula	C13H21O5P
Molar mass	288.280 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC(C)c1cccc(c1OCOP(=O)(O)O)C(C)C
InChI InChI=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) N Key:QVNNONOFASOXQV-UHFFFAOYSA-N N
NY (what is this?)  (verify)

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.^[5][6] 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]}

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.^[7]

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).^[8]

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.^[9][10] 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.^[11] 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.^[12]

Controlled substance

Fospropofol is classified as a Schedule IV controlled substance in the United States' Controlled Substances Act.^[13]

See also

• Ciprofol