Mivacurium

Mivacurium (brand name Mivacron) is a short-acting, non-depolarizing neuromuscular blocking agent used in anesthesia practice. It produces muscle relaxation by competing with acetylcholine at the neuromuscular junction.

It is primarily employed to facilitate endotracheal intubation and to provide skeletal muscle relaxation during surgical procedures or mechanical ventilation. Its rapid onset and short duration make it useful for short procedures.

Mivacurium is hydrolyzed by plasma butyrylcholinesterase (BCHE) rather than by hepatic or renal pathways, which contributes to its brief duration of action in individuals with normal enzyme activity.

The primary gene relevant to mivacurium metabolism is BCHE, which encodes butyrylcholinesterase. This enzyme in the plasma rapidly hydrolyzes mivacurium into inactive metabolites. BCHE activity determines how quickly the drug is broken down.

Variations in BCHE can lead to reduced enzyme activity (intermediate or poor metabolizers), resulting in slower drug clearance and prolonged neuromuscular blockade. Conversely, normal BCHE activity ensures typical drug processing and predictable recovery times.

Genetic variations in BCHE give rise to distinct metabolizer phenotypes (normal, intermediate, poor). Reduced enzyme function increases mivacurium plasma levels and prolongs neuromuscular blockade, raising the risk of postoperative respiratory depression and delayed recovery.

Genetic variation in BCHE alters butyrylcholinesterase enzyme activity, affecting the duration of neuromuscular blockade after mivacurium administration. Below are the expected clinical effects by metabolizer status:

Normal Metabolizer

• Effect on drug levels: Standard mivacurium metabolism resulting in normal plasma concentrations.
• Clinical consequence: Expected duration of neuromuscular blockade as per standard protocols.
• Side effects: Typical, short-lived muscle relaxation; severity and frequency as observed in the general population.

Intermediate Metabolizer

• Effect on drug levels: Moderately increased plasma concentrations due to reduced BCHE activity.
• Clinical consequence: Prolonged neuromuscular blockade requiring extended monitoring.
• Side effects: Increased risk of muscle weakness and delayed recovery; moderate frequency.

Poor Metabolizer

• Effect on drug levels: Significantly elevated plasma concentrations owing to minimal BCHE activity.
• Clinical consequence: Markedly prolonged neuromuscular blockade with potential for respiratory depression.
• Side effects: Severe and prolonged muscle paralysis; low frequency but high risk when present.

Indeterminate/Not Available

• Effect on drug levels: Unknown due to insufficient data.
• Clinical consequence: No specific guidance; standard dosing with clinical monitoring.
• Side effects: Unpredictable; monitor for prolonged muscle effects.

BCHE Dosing Guideline

Examples from guidelines include using alternative neuromuscular blocking agents not metabolized by butyrylcholinesterase, such as cisatracurium or rocuronium.

• FDA – Table of Pharmacogenetic Associations