A potentially toxic drug interaction between pethidine (meperidine) and phenobarbitone

Area of Science:

• Pharmacology
• Clinical Toxicology

Background:

• Pethidine (meperidine) is an opioid analgesic with a known metabolism pathway.
• Tolerance to pethidine can develop, requiring dose adjustments.
• Phenobarbitone is a barbiturate with known drug-metabolizing enzyme-inducing properties.

Observation:

• Concomitant administration of pethidine and phenobarbitone led to enhanced sedation in a pethidine-tolerant patient.
• Pethidine pharmacokinetics and metabolism were analyzed in patients receiving phenobarbitone and in controls.

Findings:

• Phenobarbitone significantly increases the N-demethylation of pethidine.
• This enhanced N-demethylation results in increased production of the toxic metabolite, norpethidine.
• Norpethidine accumulation is associated with enhanced central nervous system effects, including sedation.

Implications:

• Clinicians should be aware of the potential for enhanced sedation and toxicity when prescribing pethidine with phenobarbitone.
• Monitoring for increased sedation and potential adverse effects is crucial in patients on combined therapy.
• Understanding drug-drug interactions involving enzyme induction is vital for safe and effective pain management.