Racial differences in propranolol enantiomer kinetics following simultaneous i.v. and oral administration

Area of Science:

• Pharmacology
• Pharmacokinetics
• Racial and Ethnic Differences in Medicine

Background:

• Previous studies identified racial disparities in propranolol enantiomer kinetics.
• Understanding the mechanisms behind these differences is essential for personalized medicine.

Purpose of the Study:

• To comprehensively characterize propranolol pharmacokinetics in black and white subjects.
• To elucidate the underlying mechanisms contributing to observed racial differences in oral propranolol kinetics.

Main Methods:

• A study involving 12 white and 13 black healthy males, excluding poor metabolizers.
• Administration of oral propranolol (80 mg every 8 h for 16 doses) followed by an intravenous radiolabeled dose.
• Analysis of serum and urine samples using high-performance liquid chromatography (HPLC) to determine R- and S-propranolol and metabolite concentrations.

Main Results:

• Black subjects demonstrated significantly higher apparent oral clearances for both R- and S-propranolol compared to white subjects.
• Higher R- and S-propranolol clearances were observed in black individuals.
• Trends indicated higher rates of side chain oxidation, 4-hydroxylation, and R-propranolol glucuronidation in black subjects, though not statistically significant.

Conclusions:

• Elevated oral propranolol clearances in black subjects are attributed to slightly higher hepatic metabolism across major pathways.
• Increased propranolol clearances in black individuals are primarily due to enhanced hepatic metabolism, with a minor contribution from slightly higher liver blood flow.