Fospropofol

Fospropofol

File:Fospropofol disodium.png
Systematic (IUPAC) name
disodium [2,6-di(propan-2-yl)phenoxy]methyl phosphate
Clinical data
[[Regulation of therapeutic goods |Template:Engvar data]]	US FDA: Fospropofol
Pregnancy category	B
Dependence liability	unknown
Routes of administration	Intravenous
Legal status
Legal status	US: Schedule IV
Pharmacokinetic data
Protein binding	98%
Metabolism	Hepatic glucuronidation
Biological half-life	0.81 hours
Excretion	Renal
Identifiers
CAS Number	258516-87-9
ATC code	N01
PubChem	CID 3038497
Chemical data
Formula	C13H19Na2O5P
Molar mass	332.240261 g/mol[[]]

Fospropofol (trade name Lusedra) 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. 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. Often, fospropofol is administered in conjunction with an opioid such as fentanyl.

Clinical pharmacology

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.

Pharmacokinetics

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).

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. 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. 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.

Controlled substance

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

Further reading

• 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): Web Simulation of Fospropofol Pharmacokinetics. Retrieved 18 March 2008, from University of Florida Department of Anesthesiology Virtual Anesthesia Machine Web site: [1]

External links

pt:Fospropofol