Gender and PK-PD of Propofol and Cisatracurium (BIS5)
August 9, 2019 updated by: Ashraf Dahaba, MD, Medical University of Graz
Effect of Gender on the Pharmacokinetics-pharmacodynamics of Propofol and Cisatracurium Besylate
In recent years it has become clear that gender differences exist both in the pharmacokinetics and the pharmacodynamics of drugs related to the practice of anesthesia.
Differences in pharmacokinetics are more straightforward to study than differences in clinical effects.
However, isolated pharmacokinetic data are of less value if they are not accompanied by measurements of clinical effects.
Males are more sensitive than females to propofol.
It may therefore be necessary to decrease the propofol dose by 30-40% in males.
Females have 20-30% greater sensitivity to the muscle relaxant effects.
Study Overview
Detailed Description
Background: In recent years it has become clear that gender differences exist both in the pharmacokinetics and the pharmacodynamics of drugs related to the practice of anesthesia. Differences in pharmacokinetics are more straightforward to study than differences in clinical effects. However, isolated pharmacokinetic data are of less value if they are not accompanied by measurements of clinical effects. Males are more sensitive than females to propofol. It may therefore be necessary to decrease the propofol dose by 30-40% in males. Females have 20-30% greater sensitivity to the muscle relaxant effects.
Methods: Anaesthesia is induced with propofol 2 mg/kg (t0) followed by cisatracurium 0.1 mg/kg 1 min from propofol administration (t2). Patients will be monitored using the conventionally available bispectral index monitoring for propofol concentrations and Relaxometer mechanomyograph neuromuscular monitoring for cisatracurium. Serial arterial blood samples (5 ml) were withdrawn in EDTA-tubes before cisatracurium administration, 1, 3, 5, 7, 10, 13, 16, 19, 22, 25, 30, 60 and 90 min following administration. Blood samples were assayed in duplicate using high performance liquid chromatograph. Pharmacokinetic analysis was performed by fitting the cisatracurium blood concentration time profile of individual patients, to non-compartmental as well as multi-compartmental pharmacokinetic models.
Study Type
Observational
Enrollment (Actual)
120
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
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
14 years to 61 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Sampling Method
Non-Probability Sample
Study Population
differences between equal numbers of males and females
Description
Inclusion Criteria:
1. either males or females
Exclusion Criteria:
1. Liver disease
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
- Observational Models: Case-Control
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
|---|---|
|
male group
Propofol 2 mg/kg (t0) followed by cisatracurium 0.1 mg/kg 1 min (t2).
Patients will be monitored using bispectral index monitoring for propofol and Relaxometer mechanomyograph neuromuscular monitoring for cisatracurium.
Serial arterial blood samples (5 ml) were withdrawn in EDTA-tubes before cisatracurium administration, 1, 3, 5, 7, 10, 13, 16, 19, 22, 25, 30, 60 and 90 min following administration.
Blood samples were assayed in duplicate using high performance liquid chromatograph for Pharmacokinetic analysis.
|
Propofol 2 mg/kg (t0) followed by cisatracurium 0.1 mg/kg 1 min (t2).
Patients will be monitored using bispectral index monitoring for propofol and Relaxometer mechanomyograph neuromuscular monitoring for cisatracurium.
Serial arterial blood samples (5 ml) were withdrawn in EDTA-tubes before cisatracurium administration, 1, 3, 5, 7, 10, 13, 16, 19, 22, 25, 30, 60 and 90 min following administration.
Blood samples were assayed in duplicate using high performance liquid chromatograph for Pharmacokinetic analysis.
Other Names:
Propofol 2 mg/kg (t0) followed by cisatracurium 0.1 mg/kg 1 min (t2).
Patients will be monitored using bispectral index monitoring for propofol and Relaxometer mechanomyograph neuromuscular monitoring for cisatracurium.
Serial arterial blood samples (5 ml) were withdrawn in EDTA-tubes before cisatracurium administration, 1, 3, 5, 7, 10, 13, 16, 19, 22, 25, 30, 60 and 90 min following administration.
Blood samples were assayed in duplicate using high performance liquid chromatograph for Pharmacokinetic analysis.
Other Names:
|
|
female group
Propofol 2 mg/kg (t0) followed by cisatracurium 0.1 mg/kg 1 min (t2).
Patients will be monitored using bispectral index monitoring for propofol and Relaxometer mechanomyograph neuromuscular monitoring for cisatracurium.
Serial arterial blood samples (5 ml) were withdrawn in EDTA-tubes before cisatracurium administration, 1, 3, 5, 7, 10, 13, 16, 19, 22, 25, 30, 60 and 90 min following administration.
Blood samples were assayed in duplicate using high performance liquid chromatograph for Pharmacokinetic analysis.
|
Propofol 2 mg/kg (t0) followed by cisatracurium 0.1 mg/kg 1 min (t2).
Patients will be monitored using bispectral index monitoring for propofol and Relaxometer mechanomyograph neuromuscular monitoring for cisatracurium.
Serial arterial blood samples (5 ml) were withdrawn in EDTA-tubes before cisatracurium administration, 1, 3, 5, 7, 10, 13, 16, 19, 22, 25, 30, 60 and 90 min following administration.
Blood samples were assayed in duplicate using high performance liquid chromatograph for Pharmacokinetic analysis.
Other Names:
Propofol 2 mg/kg (t0) followed by cisatracurium 0.1 mg/kg 1 min (t2).
Patients will be monitored using bispectral index monitoring for propofol and Relaxometer mechanomyograph neuromuscular monitoring for cisatracurium.
Serial arterial blood samples (5 ml) were withdrawn in EDTA-tubes before cisatracurium administration, 1, 3, 5, 7, 10, 13, 16, 19, 22, 25, 30, 60 and 90 min following administration.
Blood samples were assayed in duplicate using high performance liquid chromatograph for Pharmacokinetic analysis.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
propofol elimination half life
Time Frame: before administration till 120 minutes
|
Propofol 3 mg/kg (t0) followed by cisatracurium 0.1 mg/kg 2 min (t2).
Patients will be monitored using bispectral index monitoring for propofol.
Serial arterial blood samples (5 ml) were withdrawn in EDTA-tubes before cisatracurium administration, 1, 3, 5, 7, 10, 13, 16, 19, 22, 25, 30, 60 and 90 min following administration.
Blood samples were assayed in duplicate using high performance liquid chromatograph for Pharmacokinetic analysis.
|
before administration till 120 minutes
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
cisatracurium elimination half life
Time Frame: before administration till 120 minutes
|
Propofol 3 mg/kg (t0) followed by cisatracurium 0.1 mg/kg 2 min (t2).
Patients will be monitored using TOF-Watch neuromuscular monitoring for cisatracurium.
Serial arterial blood samples (5 ml) were withdrawn in EDTA-tubes before cisatracurium administration, 1, 3, 5, 7, 10, 13, 16, 19, 22, 25, 30, 60 and 90 min following administration.
Blood samples were assayed in duplicate using high performance liquid chromatograph for Pharmacokinetic analysis.
|
before administration till 120 minutes
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Ashraf Dahaba, Medical University of Graz
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
- Schmith VD, Fiedler-Kelly J, Phillips L, Grasela TH Jr. Prospective use of population pharmacokinetics/pharmacodynamics in the development of cisatracurium. Pharm Res. 1997 Jan;14(1):91-7. doi: 10.1023/a:1012015719694.
- Vuyk J, Oostwouder CJ, Vletter AA, Burm AG, Bovill JG. Gender differences in the pharmacokinetics of propofol in elderly patients during and after continuous infusion. Br J Anaesth. 2001 Feb;86(2):183-8. doi: 10.1093/bja/86.2.183.
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
January 1, 2010
Primary Completion (Actual)
April 1, 2011
Study Completion (Actual)
April 1, 2011
Study Registration Dates
First Submitted
October 23, 2015
First Submitted That Met QC Criteria
October 24, 2015
First Posted (Estimate)
October 27, 2015
Study Record Updates
Last Update Posted (Actual)
August 12, 2019
Last Update Submitted That Met QC Criteria
August 9, 2019
Last Verified
August 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- MUGraz5
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