title: Sedation with GPI 15715, a water-soluble prodrug of propofol, using target-controlled infusion in volunteers.
abstract: GPI 15715 is the first water-soluble propofol prodrug that has been studied in humans. Present propofol lipid formulations have well known undesirable properties, for example, pain on injection and increased triglyceride concentrations. We investigated whether GPI 15715 is suitable to achieve and maintain moderate sedation for 2 h. Six male and six female volunteers received a target-controlled infusion of GPI 15715, with an initial propofol target concentration of 1.8 microg/mL and the possibility to adjust the propofol target once after 1 h. Propofol concentrations, the bispectral index, and modified Observer's Assessment of Alertness/Sedation Scale (MOAA/S) scores were monitored. The median MOAA/S score was 4 during the first hour and was 3 during the second hour of infusion. The propofol target had to be changed to 2.4 microg/mL in seven volunteers and to 3.0 microg/mL in two volunteers. A propofol concentration of 1.9 microg/mL had the highest probability to result in an MOAA/S score of 3, which corresponds with moderate sedation. We observed no serious side effects. We conclude that GPI 15715 produces excellent sedation.
authors.affiliation: *Department of Anesthesiology, University of Erlangen-Nuremberg, Erlangen, Germany; and †Guilford Pharmaceuticals Inc., Baltimore, Maryland.
authors.forename: Jörg
authors.initials: J
authors.lastname: Fechner
authors.forename: Harald
authors.initials: H
authors.lastname: Ihmsen
authors.forename: Christine
authors.initials: C
authors.lastname: Schiessl
authors.forename: Christian
authors.initials: C
authors.lastname: Jeleazcov
authors.forename: James J
authors.initials: JJ
authors.lastname: Vornov
authors.forename: Helmut
authors.initials: H
authors.lastname: Schwilden
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schüttler
mesh_terms: D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage*; D008297:Male; D015742:Propofol / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D006993:Hypnotics and Sedatives; C472965:fospropofol; D015742:Propofol