Population Pharmacokinetics/Pharmacodynamics (PK/PD) of Microemulsion Propofol in Healthy Volunteers
Summary
AquafolTM (Daewon Pharmaceutical Co., Ltd., Seoul, Korea) is a microemulsion propofol that has been developed for eliminating lipid solvent-related adverse events of long chain triglyceride emulsion (LCT) propofol (Diprivan®; AstraZeneca, London, United Kingdom), such as infection, fat embolism, hypertriglyceridemia and pancreatitis. Originally, AquafolTM was formulated with 8% polyethylene glycol 660 hydroxystearate (Solutol HS 15, BASF Company Ltd., Seoul, Korea) and 5% tetrahydrofurfuryl alcohol polyethylene glycol ether (Glycofurol, Roche, Basle, Switzerland). A phase 1 study to assess the safety and tolerability of polymeric vehicles of this formulation in healthy volunteers showed dose-limiting toxicity. Subsequently, it was reformulated with 10% purified poloxamer 188 (PP188) as a nonionic block copolymer surfactant and 0.7% polyethylene glycol 660 hydroxystearate as a nonionic surfactant. Alterations in propofol formulation may result in altered pharmacokinetic, pharmacodynamic characteristics. The aim of this study was to compare the pharmacokinetics and pharmacodynamics of propofol microemulsion and lipid emulsion, using noncompartmental analysis and population analysis with mixed effects modeling.
Timeline
- Start
- 2009-05
- Primary completion
- 2010-05
- Completion
- 2011-06
Publications
- Background Kim KM, Choi BM, Park SW, Lee SH, Christensen LV, Zhou J, Yoo BH, Shin HW, Bae KS, Kern SE, Kang SH, Noh GJ. Pharmacokinetics and pharmacodynamics of propofol microemulsion and lipid emulsion after an intravenous bolus and variable rate infusion. Anesthesiology. 2007 May;106(5):924-34. doi: 10.1097/01.anes.0000265151.78943.af.
- Background Lee EH, Lee SH, Park DY, Ki KH, Lee EK, Lee DH, Noh GJ. Physicochemical properties, pharmacokinetics, and pharmacodynamics of a reformulated microemulsion propofol in rats. Anesthesiology. 2008 Sep;109(3):436-47. doi: 10.1097/ALN.0b013e318182a486.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Propofol | Small molecule | 1.5 mg/kg | Other |
| Subject | Propofol | Small molecule | 3 mg/kg | Other |
| Subject | Propofol | Small molecule | 6 mg/kg | Other |
| Subject | Propofol | Small molecule | 12 mg/kg | Other |
Indications
No indication recorded.