Hemodynamic profile in rabbits of fospropofol disodium injection relative to propofol emulsion following rapid bolus injection

Michelle Paula McIntosh, Ken Iwasawa, Roger A Rajewski, Tatsuro Fujisawa, Hiroshi Goto

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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.
Original languageEnglish
Pages (from-to)3518 - 3525
Number of pages8
JournalJournal of Pharmaceutical Sciences
Issue number9
Publication statusPublished - 2012

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