Chemistry:Fospropofol
Fospropofol (INN[1]), often used as the disodium salt (trade name Lusedra[2]) 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.[3][4] 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.{{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.[5]
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).[6]
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.[7][8] 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.[9] 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.[10]
Controlled substance
Fospropofol is classified as a Schedule IV controlled substance in the United States' Controlled Substances Act.[11]
See also
References
- ↑ "Recommended INNs 2006, pt 56". https://www.who.int/entity/medicines/publications/druginformation/innlists/RL56.pdf?ua=1.
- ↑ "FDA Approves Fospropofol and Follows ASAs Labeling Recommendation". American Society of Anesthesiologists. 2008-12-15. http://www.asahq.org/news/asanews121508.htm.
- ↑ "Water-soluble propofol analogues with intravenous anaesthetic activity". Bioorganic & Medicinal Chemistry Letters 11 (7): 927–930. April 2001. doi:10.1016/S0960-894X(01)00088-9. PMID 11294393.
- ↑ "Novel water soluble 2,6-dimethoxyphenyl ester derivatives with intravenous anaesthetic activity". Bioorganic & Medicinal Chemistry Letters 13 (12): 1971–1975. June 2003. doi:10.1016/S0960-894X(03)00346-9. PMID 12781176.
- ↑ "Fospropofol: pharmacokinetics?". Journal of Anaesthesiology Clinical Pharmacology 28 (1): 134–135. January 2012. doi:10.4103/0970-9185.92472. PMID 22345970.
- ↑ "Pharmacokinetic and pharmacodynamic characteristics of medications used for moderate sedation". Clinical Pharmacokinetics 45 (9): 855–869. 2006. doi:10.2165/00003088-200645090-00001. PMID 16928150.
- ↑ "Pharmacokinetics and pharmacodynamics of GPI 15715 or fospropofol (Aquavan injection) - a water-soluble propofol prodrug". Modern Anesthetics. Handbook of Experimental Pharmacology. 182. 2008. pp. 253–66. doi:10.1007/978-3-540-74806-9_12. ISBN 978-3-540-72813-9.
- ↑ "Fospropofol assay: issues and impact on pharmacokinetic and pharmacodynamic evaluation". European Journal of Anaesthesiology 26 (1): 81; discussion 81-81; discussion 82. January 2009. doi:10.1097/EJA.0b013e32831bc285. PMID 19122558.
- ↑ "Propofol Monograph for Professionals". 2024-06-10. https://www.drugs.com/monograph/propofol.html.
- ↑ "LUSEDRA (fospropofol disodium) Injection, for intravenous use". https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022244lbl.pdf.
- ↑ "Schedule of Controlled Substances; Placement of Fospropofol into Schedule IV ," 74 Federal Register 192 (October 6, 2009), pp. 51234–51236.
 |  |
