Sex-related Differences in the Response to the Muscle Relaxant Drug Mivacurium

The Pharmacodynamics of Mivacurium in Males and Females: A Study in Human Volunteers

Muscle relaxants are drugs providing muscle relaxation during surgical treatment. Previous studies have shown that males and females respond differently to this kind of drug. Our hypothesis is that males are more sensitive to the effect of Mivacurium (a muscle relaxant) than females, meaning that males need a lower blood concentration of the drug than females in order to obtain a given effect.

Study Overview

• Status: Completed
• Conditions: Muscle Relaxation; Sex
• Intervention / Treatment: Drug: Mivacurium

Detailed Description

Muscle relaxants are a type of drug used to provide muscle relaxation during induction of anesthesia and surgical treatment. Residual drug effect postoperatively (i.e. residual muscle relaxation) occurs frequently and studies have shown that this may be harmful in certain groups of patients. Of special concern is residual effect on upper airway and breathing muscles. A previous study has shown that males and females respond differently to the effect of this kind of drug. It appears that some muscle groups which are important for airway protection and breathing are more sensitive to the effect of muscle relaxants in males than females. Males may therefore be more susceptible to postoperative lung complications than females. In this study we try to determine what causes the observed sex-related difference in response to the muscle relaxant Mivacurium. We have previously shown that this sex-related difference cannot be explained by different pharmacokinetics (what the body does to the drug) in males and females. Our hypothesis is that a pharmacodynamic (what the drug does to the body) difference between sexes exists, i.e. that a lower blood concentration of Mivacurium is needed in males than females in order to obtain a predefined degree of muscle relaxation in certain muscle groups.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94131
      • University of California, UCSF

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria: Healthy individuals with no current medication -

Exclusion Criteria: Previous complications during anesthesia, pregnancy, allergy to muscle relaxants, smoking, gastrointestinal reflux.

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Males vs females; Constant-rate IV infusions of Mivacurium, range 1.0 - 3 micro/kg/min, duration 150 - 180 min	Drug: Mivacurium; Effect of Mivacurium in males vs females; Other Names: Mivacron

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamics of Mivacurium	The mivacurium drug concentration in the blood associated with 50% of maximal drug effect at steady-state conditions (Css50) will be determined at the thumb and the handgrip muscles.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clearance of Mivacurium	Clearance calculated as the relationship between steady-state infusion rate of Mivacurium and Mivacurium blood concentration.	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relationship between thumb acceleration (TOF ratio) and handgrip strength in both sexes	Thumb acceleration secondary to nerve stimulation at the ulnar nerve (TOF ratio) is an objective way of monitoring the effect of muscle relaxants that is used frequently during clinical anesthesia. Handgrip strength will be monitored with a dynamometer.	6 months

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: Oslo University Hospital
• Investigators: Principal Investigator: John R Feiner, MD, University of California, UCSF, San Francisco, USA

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): July 1, 2013

Study Registration Dates

• First Submitted: July 17, 2013
• First Submitted That Met QC Criteria: July 20, 2013
• First Posted (Estimate): July 24, 2013

Study Record Updates

• Last Update Posted (Estimate): April 11, 2014
• Last Update Submitted That Met QC Criteria: April 9, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: Sensitivity; Sex; Mivacurium; Nondepolarizing neuromuscular blocking drug
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Neuromuscular Agents; Neuromuscular Nondepolarizing Agents; Neuromuscular Blocking Agents; Mivacurium
• Other Study ID Numbers: IRB11-07970