Fospropofol disodium (Lusedra®)
Chemistry:
➧ The chemical nature of propofol is 2,6-diisopropyl phenol. When a phosphate group is added to this molecule, it results in the formation of water-soluble propofol that does not contain lipids, egg products, or preservatives, thereby eliminating the allergic, bacterial infections and hyperlipidemic concerns associated with propofol.
➧ The two phosphorylated propofol prodrugs were named propofol phosphate and phosphonooxymethyl propofol.
➧ Substitution of hydroxyl by charged phosphate group introduces electronegativity which allows fospropofol to dissolve readily in water, hence does not cross the lipid membrane. The sodium salt of fospropofol is commonly used (2,6-diisopropyl phenoxy methyl phosphate disodium salt).
Mechanism of Action:
➧ Fospropofol is a water-soluble prodrug of propofol, a sedative/hypnotic/anesthetic drug. it is hydrolyzed by endothelial alkaline phosphatases to an active metabolite, propofol, formaldehyde, and phosphate, this process takes 15-20 min. leading to slow onset of action (4-13 min.). Its mechanism of action is uncertain, but it is postulated that its primary effect may be potentiation of the GABA-A and glycine receptors, possibly by slowing the channel closing time.
Uses:
➧ Fospropofol is an intravenous sedative-hypnotic agent. It is currently approved for use in monitored anesthesia care sedation of adult patients undergoing diagnostic or therapeutic procedures such as endoscopy.
Formulation and dose:
➧ Fospropofol is supplied as an aqueous solution designed for intravenous injection. The recommended initial dose of the drug is as follows:
Standard Dosing Regimen:
➧ In adults aged 18 to <65 years, who are healthy or have mild systemic disease, an initial IV bolus of 6.5 mg/kg followed by supplemental IV doses of 1.6 mg/kg (25 % of initial dosage) as needed to achieve the desired level of sedation.
➧ The dosage of fospropofol is limited by the lower and upper weights of 60 kg and 90 kg.
Modified Dosing Regimen:
➧ For adults>65 years of age or those with severe systemic disease, initial and supplemental IV dosages of 75 % of the standard dosing regimen.
Advantages:
1-Less pain at the site of IV administration.
2-Less potential for hyperlipidemia with long-term administration.
3-Less chance for bacteremia.
Side Effects:
➧ Adverse events associated with the use of fospropofol may include, but are not limited to, the following:
1-Paresthesias
2-Pruritus
3-Hypotension
4-Hypoxemia
5-Nausea
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