The Pharmacokinetics and Pharmacodynamics of Propofol in a Modified Cyclodextrin Formulation (Captisol??) Versus Propofol in a Lipid Formulation (Diprivan??): An Electroencephalographic and Hemodynamic Study in a Porcine Model

Abstract

A modified cyclodextrin-based formulation of propofol has been developed that may mitigate some of the problems associated with propofol in lipid emulsion. However, reformulation of propofol may change its clinical characteristics. This study in a pig model showed that the novel propofol formulation was substantially similar to the lipid emulsion propofol formulation.

A Phase 1c Trial Comparing the Efficacy and Safety of a New Aqueous Formulation of Alphaxalone With Propofol

“…This difference occurred even though the same depth and duration of cortical depression was present in both treatment groups evidenced by the same BIS values shown in Figure 3. The maximum decreases in systolic blood pressure, median (IQR), were 12 (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) mm Hg for PHAX and 25 (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28) mm Hg for propofol and diastolic blood pressure were 14 (9-16) mm Hg for PHAX and 26 (22)(23)(24)(25)(26)(27)(28)(29)(30) mm Hg for propofol. Further, these differences in pressure occurred when the heart rate increases after administration of anesthetic injection, median (IQR) were: 21 (16-24) beats/minute for PHAX and 15 (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)…”

“…[23][24][25][26][27] It has not been previously investigated as an excipient for alphaxalone. Such a preparation, alphaxalone in aqueous solution with SBECD, Phaxan™ (PHAX), has been made and tested in preclinical studies.…”

Accuracy of target-controlled infusion (TCI) with 2 different propofol formulations

“…Dass die Galenik die Pharmakologie von Propofol beeinflussen könnte, wurde bereits früher diskutiert. Während bei Ratten für fettfreies Propofol eine deutlich veränder-te Pharmakokinetik mit größerem Verteilungsvolumen gefunden wurde [5], zeigten sich im Tierversuch keine Unterschiede, wenn man Propofol mit unterschiedlichen Fettemulsionen [3] oder mit der Trä-gersubstanz Cyclodextrin applizierte [6]. In Probanden und Patienten wurden ebenfalls verschiedene Propofolformulierungen untersucht, die sich gegenüber Disoprivan ® v. a durch die Verwendung mittelkettiger Triglyzeride unterscheiden [4, 9, 7, 20] …”

Pharmacokinetics and Pharmacodynamics of GPI 15715 or Fospropofol (Aquavan Injection) — A Water-Soluble Propofol Prodrug

“…Therefore during the last several years there has been considerable interest in the development of new propofol formulations or a propofol prodrug. The first reports of propofol in aqueous solutions with the solvent propylene glycol, hydroxy-β-cyclodextrin or 2-hydroxypropyl-γ-cyclodextrin have been published (Egan et al 2003;Trapani et al 2004). A propofol micro-emulsion with the solvent Poloxamer 188 (BASF Company, Florham Park, NJ) has been tested in an animal model in dogs (Morey et al 2006) and a propofol micro-emulsion with the solvent propylene glycol 660 hydroxystearate (Solutol HS 15, BASF Company, Seoul) has been tested in the first study for anaesthesia in man (Kim et al 2007).…”