Fospropofol

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; 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.

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.

References

References

1. "Fospropofol disodium". U.S. National Library of Medicine.
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6. (June 2003). "Novel water soluble 2,6-dimethoxyphenyl ester derivatives with intravenous anaesthetic activity". Bioorganic & Medicinal Chemistry Letters.
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8. (2006). "Pharmacokinetic and pharmacodynamic characteristics of medications used for moderate sedation". Clinical Pharmacokinetics.
9. (2008). "Modern Anesthetics".
10. (January 2009). "Fospropofol assay: issues and impact on pharmacokinetic and pharmacodynamic evaluation". European Journal of Anaesthesiology.
11. (2024-06-10). "Propofol Monograph for Professionals".
12. "LUSEDRA (fospropofol disodium) Injection, for intravenous use".
13. "[http://edocket.access.gpo.gov/2009/pdf/E9-23971.pdf Schedule of Controlled Substances; Placement of Fospropofol into Schedule IV]{{Dead link. (December 2019)