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

January 18, 2012 updated by: Gyu-Jeong Noh, Asan Medical Center

Population Pharmacokinetic and Pharmacodynamic Modeling of Microemulsion Propofol in Healthy Volunteers: Comparison With Lipid Emulsion Propofol

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

63

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
Between 5/2/2009 until 5/31/2010

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2009

Primary Completion (Actual)

May 1, 2010

Study Completion (Actual)

June 1, 2011

Study Registration Dates

First Submitted

May 22, 2009

First Submitted That Met QC Criteria

May 26, 2009

First Posted (Estimate)

May 27, 2009

Study Record Updates

Last Update Posted (Estimate)

January 20, 2012

Last Update Submitted That Met QC Criteria

January 18, 2012

Last Verified

January 1, 2012

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Microemulsion Phase 1

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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