Population Pharmacokinetics/Pharmacodynamics (PK/PD) of Microemulsion Propofol in Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gyu-Jeong Noh, Asan Medical Center
ClinicalTrials.gov Identifier:
NCT00908726
First received: May 22, 2009
Last updated: January 18, 2012
Last verified: January 2012
  Purpose

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.


Condition Intervention Phase
Healthy
Drug: propofol
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Population Pharmacokinetic and Pharmacodynamic Modeling of Microemulsion Propofol in Healthy Volunteers: Comparison With Lipid Emulsion Propofol

Resource links provided by NLM:


Further study details as provided by Asan Medical Center:

Primary Outcome Measures:
  • The aim of this study was to compare the pharmacokinetics and pharmacodynamics of microemulsion and lipid emulsion propofol. [ Time Frame: Between 5/2/2009 until 5/31/2010 ] [ Designated as safety issue: Yes ]

Enrollment: 63
Study Start Date: May 2009
Study Completion Date: June 2011
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Microemulsion propofol Drug: propofol
Each subject received both propofol formulations in a crossover fashion separated by a 7-day washout period, and the order of the drug administration was randomized. Subjects received both propofol formulations (Lipid emulsion propofol: Diprivan® and Microemulsion propofol: AquafolTM) during 60 min. The infusion rate was assigned according to a nonblinded, randomized design to 1.5, 3, 6, or 12 mg/kg/hr.
Other Names:
  • Microemulsion propofol: AquafolTM
  • Lipid emulsion propofol: Diprivan®
Active Comparator: Lipid emulsion propofol Drug: propofol
Each subject received both propofol formulations in a crossover fashion separated by a 7-day washout period, and the order of the drug administration was randomized. Subjects received both propofol formulations (Lipid emulsion propofol: Diprivan® and Microemulsion propofol: AquafolTM) during 60 min. The infusion rate was assigned according to a nonblinded, randomized design to 1.5, 3, 6, or 12 mg/kg/hr.
Other Names:
  • Microemulsion propofol: AquafolTM
  • Lipid emulsion propofol: Diprivan®

Detailed Description:

The Subjects fasted for 6 h before study drug administration. An 18-gauge angiocatheter was placed in a vein of the antecubital area. A second angiocatheter was placed in the contralateral radial artery for frequent blood sampling. Subjects were monitored with electrocardiography, pulse oximetry, end-tidal carbon dioxide concentration, and invasive blood pressure measurement (Datex-Ohmeda S/5;Planar Systems, Inc., Beaverton, OR) and Bispectral Index (BIS) (Aspect 2000; Aspect Medical Systems, Inc., Newton,MA). In addition, the electroencephalographic activity of seven monopolar channels (Fp1, Fp2, F3, F4, Cz, P3, and P4, referenced by A2) was recorded by QEEG-8 (LXE3208, Laxtha Inc., Daejeon, Korea).

The subjects were stratified into three age groups (19-40, 41-64, and > 65 yr), and each group included 10 male and 10 female volunteers. Each subject received both propofol formulations in a crossover fashion separated by a 7-day washout period, and the order of the drug administration was randomized. Subjects received both propofol formulations during 60 min. The infusion rate was assigned according to a nonblinded, randomized design to 1.5, 3, 6, or 12 mg/kg/hr.

Samples were collected in ethylenediaminetetraacetic acid (EDTA) tube and centrifuged for 10 min at 3,500rpm. Plasma was stored at -70°C until assay. Arterial blood samples (4 ml) were taken at preset intervals: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 15, 20, 30, 40, 50, 58, 60, 62, 66, 70, 80, 90, 120 and 150 min after administration of propofol. Venous blood samples (4ml) were taken at preset intervals: 180, 240, 300, 600, 720 and 1,200 min after administration of propofol. In addition, arterial samples were drawn when LOC (loss of consciousness) and ROC (recovery of consciousness) were observed.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • ASA 1 or 2 (healthy or mild systemic illness) healthy volunteers
  • age ≥ 19 yr

Exclusion Criteria:

  • ASA 3 or above
  • out with age group above
  • contraindications against the use of propofol
  • abnormal laboratory finding with clinical significance
  • evidence of pregnancy
  • history of alcohol or drug abuse
  • neurological or psychiatric disease
  • unable or unwilling to give informed consent
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00908726

Locations
Korea, Republic of
Asan Medical Center
Seoul, Korea, Republic of, 138-736
Sponsors and Collaborators
Asan Medical Center
Investigators
Study Chair: Gyu-Jeong Noh, M.D. & Ph.D. Professor & Chairperson, Department of Clinical Pharmacology and Therapeutics, Asan Medical Center
Principal Investigator: Byung-Moon Choi, M.D. Staff Anesthesiologist, Department of Anesthesiology and Pain Medicine, National Medical Center
  More Information

Publications:
Responsible Party: Gyu-Jeong Noh, Professor of department of anesthesiology and pain medicine, and Clinical pharamcology, Asan Medical Center
ClinicalTrials.gov Identifier: NCT00908726     History of Changes
Other Study ID Numbers: Microemulsion Phase 1
Study First Received: May 22, 2009
Last Updated: January 18, 2012
Health Authority: Korea: Food and Drug Administration

Additional relevant MeSH terms:
Propofol
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Hypnotics and Sedatives

ClinicalTrials.gov processed this record on July 22, 2014