Fospropofol - Intravenous Anesthetics

FOSPROPOFOL

As previously noted, injection pain during administration of propofol is often perceived as severe, and the lipid emulsion has several disadvantages. Intense research has focused on finding alternative formulations or related drugs that would address some of these problems. Fospropofol is a water-soluble prodrug of propofol, chemically described as 2,6-diisopropylphenoxymethyl phosphate disodium salt, that was licensed by the Food and Drug Administration in 2008 as a sedating agent for use in adult patients during monitored anesthesia care. The prodrug is rapidly metabolized by alkaline phosphatase, producing propofol, phos-phate, and formaldehyde. The formaldehyde is metabolized by aldehyde dehydrogenase in the liver and in erythrocytes. The available fospropofol formulation is a sterile, aqueous, colorless, and clear solution that is supplied in a single-dose vial at a concen-tration of 35 mg/mL under the trade name Lusedra.

Pharmacokinetics & Organ System Effects

Because the active compound is propofol and fospropofol is a prodrug that requires metabolism to form propofol, the pharma-cokinetics are more complex than for propofol itself. Multi-compartment models with two compartments for fospropofol and three for propofol have been used to describe the kinetics.

The effect profile is similar to that of propofol, but onset and recovery are prolonged compared with propofol because the pro-drug must first be converted into an active form. Although patients receiving fospropofol do not appear to experience the injection pain typical of propofol, a common adverse effect is the experience of paresthesia, often in the perianal region, which occurs in up to 74% of patients. The mechanism for this effect is unknown.

Clinical Uses & Dosage

Fospropofol is approved for sedation during monitored anesthesia care. Supplemental oxygen must be administered to all patients receiving the drug. As with propofol, airway compromise is a major concern. Hence, it is recommended that fospropofol be adminis-tered only by personnel trained in airway management. The rec-ommended standard dosage is an initial bolus dose of 6.5 mg/kg IV followed by supplemental doses of 1.6 mg/kg IV as needed. For patients weighing more than 90 kg or less than 60 kg, 90 or 60 kg should be used to calculate the dose, respectively. The dose should be reduced by 25% in patients older than 65 years and in those with an American Society of Anesthesiologists status of 3 or 4.