Fospropofol ( INN), often used as the disodium salt (trade name Lusedra) is an

intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...

sedative A sedative or tranquilliser is a substance that induces sedation by reducing irritability or Psychomotor agitation, excitement. They are central nervous system (CNS) Depressant, depressants and interact with brain activity, causing its decelera ...

hypnotic A hypnotic (from Ancient Greek, Greek ''Hypnos'', sleep), also known as a somnifacient or soporific, and commonly known as sleeping pills, are a class of psychoactive drugs whose primary function is to sleep induction, induce sleep and to trea ...

agent. It is currently approved for use in sedation of adult patients undergoing

diagnostic Diagnosis (: diagnoses) is the identification of the nature and cause of a certain phenomenon. Diagnosis is used in a lot of different academic discipline, disciplines, with variations in the use of logic, analytics, and experience, to determine " ...

or therapeutic procedures such as

endoscopy An endoscopy is a procedure used in medicine to look inside the body. The endoscopy procedure uses an endoscope to examine the interior of a hollow organ or cavity of the body. Unlike many other medical imaging techniques, endoscopes are insert ...

Clinical applications

Several

water-soluble In chemistry, solubility is the ability of a substance, the solute, to form a solution with another substance, the solvent. Insolubility is the opposite property, the inability of the solute to form such a solution. The extent of the solub ...

derivatives and

prodrug A prodrug is a pharmacologically inactive medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be ...

s of the widely used intravenous anesthetic agent

propofol Propofol is the active component of an intravenous anesthetic formulation used for induction and maintenance of general anesthesia. It is chemically termed 2,6-diisopropylphenol. The formulation was approved under the brand name Diprivan. Nu ...

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 A chemical compound is a chemical substance composed of many identical molecules (or molecular entities) containing atoms from more than one chemical element held together by chemical bonds. A molecule consisting of atoms of only one element ...

include less pain at the site of intravenous administration, less potential for

hyperlipidemia Hyperlipidemia is abnormally high levels of any or all lipids (e.g. fats, triglycerides, cholesterol, phospholipids) or lipoproteins in the blood. citing: and The term ''hyperlipidemia'' refers to the laboratory finding itself and is also use ...

with long-term administration, and less chance for

bacteremia Bloodstream infections (BSIs) are infections of blood caused by blood-borne pathogens. The detection of microbes in the blood (most commonly accomplished by blood cultures) is always abnormal. A bloodstream infection is different from sepsis, wh ...

. Often, fospropofol is administered in conjunction with an opioid such as fentanyl.

Clinical pharmacology

Mechanism of action

Fospropofol is a prodrug of propofol; as an

organophosphate In organic chemistry, organophosphates (also known as phosphate esters, or OPEs) are a class of organophosphorus compounds with the general structure , a central phosphate molecule with alkyl or aromatic substituents. They can be considered ...

it is metabolized by

alkaline phosphatase The enzyme alkaline phosphatase (ALP, alkaline phenyl phosphatase, also abbreviated PhoA) is a phosphatase with the physiological role of dephosphorylating compounds. The enzyme is found across a multitude of organisms, prokaryotes and eukaryo ...

s to

phosphate Phosphates are the naturally occurring form of the element phosphorus. In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthop ...

and

formaldehyde Formaldehyde ( , ) (systematic name methanal) is an organic compound with the chemical formula and structure , more precisely . The compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde. It is stored as ...

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.

Distribution

Following the administration of fospropofol 12.5 mg/kg (the maximum recommended dose)

loss of consciousness Unconsciousness is a state in which a living individual exhibits a complete, or near-complete, inability to maintain an awareness of self and environment or to respond to any human or environmental stimulus. Unconsciousness may occur as the re ...

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 The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

by alkaline phosphatases to propofol,

, and

. 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 In mathematics, two set (mathematics), sets or class (mathematics), classes ''A'' and ''B'' are equinumerous if there exists a one-to-one correspondence (or bijection) between them, that is, if there exists a function (mathematics), function from ...

dose of propofol and also that its clinical effect is more sustained. These features can be desirable for endoscopic procedures such as

esophagogastroduodenoscopy Esophagogastroduodenoscopy (EGD) or oesophagogastroduodenoscopy (OGD), also called by various other names, is a diagnostic endoscopic procedure that visualizes the upper part of the gastrointestinal tract down to the duodenum. It is considered ...

colonoscopy Colonoscopy () or coloscopy () is a medical procedure involving the Endoscopy, endoscopic examination of the large bowel (colon) and the distal portion of the small bowel. This examination is performed using either a Charge-coupled device, CCD ...

, bronchoscopy, as well as for some surgical procedures done under

local Local may refer to: Geography and transportation * Local (train), a train serving local traffic demand * Local, Missouri, a community in the United States Arts, entertainment, and media * ''Local'' (comics), a limited series comic book by Bria ...

regional In geography, regions, otherwise referred to as areas, zones, lands or territories, are portions of the Earth's surface that are broadly divided by physical characteristics (physical geography), human impact characteristics (human geography), and ...

anesthesia. Propofol is further metabolised to propofol

glucuronide A glucuronide, also known as glucuronoside, is any substance produced by linking glucuronic acid to another substance via a glycosidic bond. The glucuronides belong to the glycosides. Glucuronidation, the conversion of chemical compounds to glucu ...

(34.8%) and

quinol Hydroquinone, also known as benzene-1,4-diol or quinol, is an aromatic organic compound that is a type of phenol, a derivative of benzene, having the chemical formula C6H4(OH)2. It has two hydroxyl groups bonded to a benzene ring in a ''para' ...

glucuronide. Formaldehyde is a known

carcinogen A carcinogen () is any agent that promotes the development of cancer. Carcinogens can include synthetic chemicals, naturally occurring substances, physical agents such as ionizing and non-ionizing radiation, and biologic agents such as viruse ...

but label information states that serum formaldehyde levels are similar to background levels. No long term studies have been done on the

cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

risks. The parent drug has a terminal

elimination half-life Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the blood plasma. ...

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 The Controlled Substances Act (CSA) is the statute establishing federal government of the United States, federal drug policy of the United States, U.S. drug policy under which the manufacture, importation, possession, use, and distribution of ...

.Schedule of Controlled Substances; Placement of Fospropofol into Schedule IV
" 74 Federal Register 192 (October 6, 2009), pp. 51234–51236.

References

{{GABAAR PAMs General anesthetics Sedatives Phenol ethers Prodrugs GABAA receptor positive allosteric modulators Isopropyl compounds Phosphate esters