title: Hemodynamic profile in rabbits of fospropofol disodium injection relative to propofol emulsion following rapid bolus injection.
abstract: The effects of aqueous fospropofol disodium (FP) and propofol emulsion (PE) on hemodynamics and sympathetic nerve activity in rabbits following bolus injection were evaluated. Barodenervated and neuraxis-intact rabbits received PE at 4 mg/kg (PE(4)) or FP equal to 4 or 8 mg/kg propofol equivalents (FP(4) and FP(8), respectively) intravenously as a rapid bolus injection, and mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) were recorded for 20 min. The plasma propofol pharmacokinetic behavior from FP and PE was evaluated to support the pharmacodynamic observations. In barodenervated animals, MAP and RSNA decreased significantly in all groups (PE(4) > FP(8) > FP(4)). HR decreased only in the PE(4) group. The time for the maximum reduction of MAP was significantly longer with FP(8) compared with PE(4). MAP decreased, and RSNA and HR increased significantly in the neuraxis-intact animals (PE(4) > FP(8) > FP(4)). The time for maximum reduction of MAP was essentially the same in all neuraxis-intact groups. Plasma propofol levels from FP were lower than those from PE in the first 4 min following administration. The results suggest that the tachycardia observed in humans following injection of FP is not a direct physiological effect of the agent.
authors.affiliation: Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.
authors.forename: Michelle P
authors.initials: MP
authors.lastname: McIntosh
authors.forename: Ken
authors.initials: K
authors.lastname: Iwasawa
authors.forename: Roger A
authors.initials: RA
authors.lastname: Rajewski
authors.forename: Tatsuro
authors.initials: T
authors.lastname: Fujisawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Goto
mesh_terms: D018686:Anesthetics, Intravenous / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004655:Emulsions; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007275:Injections, Intravenous; D007668:Kidney / Q000294:innervation; D011311:Pressoreceptors / Q000601:surgery; D011355:Prodrugs / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D015742:Propofol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D011817:Rabbits; D013562:Sympathectomy; D013564:Sympathetic Nervous System / Q000187:drug effects; D013610:Tachycardia / Q000139:chemically induced / Q000503:physiopathology
chemical_list: D018686:Anesthetics, Intravenous; D004655:Emulsions; D011355:Prodrugs; C472965:fospropofol; D015742:Propofol