Fospropofol Disodium for Procedural Sedation: Emerging Evidence of its Value?

Abstract

Background Fospropofol is a phosphate-ester water soluble prodrug of propofol approved in the United States for the short-term sedation of adults undergoing diagnostic or therapeutic procedures with monitored anesthesia care. Fospropofol may be advantageous for procedural sedation because it is not a lipid formulation, it lacks pain on injection, it possesses a different pharmacokinetic profile due to in vivo conversion of fospropofol to propofol, and it offers rapid recovery from sedation. Objective To review published pharmacokinetic data, clinical trials, and the safety profile of fospropofol and provide comment on its use for sedation. Clinical trials Fospropofol has been studied for sedation in colonoscopy and bronchoscopy with fentanyl for analgesia. Results indicate that a 6.5 mg/kg bolus dose with repeated doses of 25% of the original bolus dose up to every 4 minutes produces an effective and safe level of sedation. Fospropofol comparisons to midazolam were not assessed. Patient satisfaction is high for those treated with the recommended dosage regimen. Most commonly reported adverse effects included pruritus and paresthesia. Sedation related side effects such as hypoxia and apnea were rarely reported and generally mild in scope. Conclusion Fospropofol represents an alternative sedative agent to midazolam and propofol for short-term sedation. However, the efficacy and safety of fospropofol compared to midazolam or propofol has not been assessed, therefore use will be based on practitioner preference. Restrictive package labelling requiring MAC poses medico-legal and cost-benefit issues thereby not conferring a benefit over propofol which caries similar labelling. Additional studies designed to compare fospropofol to propofol and/or midazolam for procedural sedation are needed.

The Prodrug Approach: A Successful Tool for Improving Drug Solubility

“…The aqueous solubility of fospropofol provides an advantage over propofol, which is available only as a lipid-containing oil-water emulsion. These advantages include lack of pain on injection, different pharmacokinetic profile due to in vivo conversion of fospropofol to propofol and rapid recovery from sedation [121,122].…”

Gastrointestinal delivery of propofol from fospropofol: its bioavailability and activity in rodents and human volunteers

“…In spite of this potentially useful and unique pharmacology, the clinical use of propofol in other therapeutic areas has been limited by its formulation as a short-acting intravenous emulsion. Propofol’s insolubility in water requires its formulation in a lipid emulsion [ 18 ] using complicated manufacturing processes with ensuing limited storage time because of the risk of microbial contamination [ 19 ]. Propofol is not orally bioavailable in animals or in humans [ 20 , 21 ] possibly due to limited aqueous solubility, and first pass metabolism by the liver.…”

Fospropofol

“…[ 3 ] It is a water-soluble prodrug of propofol. [ 4 ] According to the American Society of Anesthesiologists (ASA), MAC is a planned procedure during which the patient undergoes local anesthesia together with sedation and analgesia. [ 5 ] It allows for the safe administration of a maximal depth of sedation in an excess of that provided during moderate sedation.…”

“…[ 9 ] The aqueous solubility of fospropofol provides an advantage over propofol which is available only as a lipid containing oil–water emulsion. [ 4 ] However, propofol has become the most popular intravenous anesthetic for making the patients subjectively feel better in the immediate post-operative period because of reduced nausea and vomiting. However, when administered for prolonged infusions, propofol can lead to delayed arousal due to its cumulative effects.…”