Propranolol reduces bupivacaine clearance.

Area of Science:

• Pharmacology
• Clinical Toxicology

Background:

• Propranolol is known to reduce lidocaine clearance.
• The effect of propranolol on bupivacaine clearance was previously uninvestigated.

Purpose of the Study:

• To investigate whether propranolol reduces the clearance of bupivacaine.
• To assess the impact of propranolol on bupivacaine metabolism and elimination.

Main Methods:

• Six healthy volunteers received intravenous bupivacaine (30-50 mg) on two occasions.
• One occasion involved prior oral administration of propranolol (40 mg every 6 h for 24 h).
• Bupivacaine clearance, elimination rate, and volume of distribution were determined from 22 blood samples over 36 hours.

Main Results:

• Mean bupivacaine clearance was reduced by 35% during propranolol use (0.21 L/min vs. 0.33 L/min control, P < 0.01).
• The terminal elimination rate constant decreased significantly, extending the half-life from 2.6 to 4.9 hours.
• Volume of distribution remained unchanged; CNS toxicity was observed at peak concentrations.

Conclusions:

• Propranolol significantly inhibits bupivacaine metabolism, likely at the hepatocyte level, rather than by reducing hepatic blood flow.
• Concomitant use of propranolol may lead to the accumulation of toxic bupivacaine concentrations.
• Clinical monitoring is advised when co-administering propranolol and bupivacaine.