Polymorphic acetylation of procaine amide in healthy subjects

Area of Science:

• Pharmacogenetics
• Drug Metabolism
• Biochemistry

Background:

• Procaine amide is an antiarrhythmic drug.
• Drug acetylation is a key metabolic pathway influenced by genetic factors.
• Understanding individual differences in drug metabolism is crucial for personalized medicine.

Purpose of the Study:

• To investigate the acetylation of procaine amide in healthy human volunteers.
• To determine if procaine amide acetylation is subject to genetic polymorphism.
• To correlate acetylator phenotype with procaine amide metabolic profiles.

Main Methods:

• Gas-liquid chromatography was employed to quantify procaine amide metabolites.
• Acetylator phenotype was assessed using sulphapyridine as a probe drug.
• Urine samples were analyzed for unchanged and acetylated forms of both drugs.

Main Results:

• Significant differences were observed in the excretion of acetylated procaine amide between slow and rapid acetylators.
• Slow acetylators excreted 9 ± 1% acetylated procaine amide, while rapid acetylators excreted 19 ± 4%.
• This indicates a slower acetylation rate for procaine amide in slow acetylators.

Conclusions:

• The acetylation of procaine amide appears to be genetically controlled.
• Procaine amide acetylation likely follows the same polymorphic pathway as isoniazid and certain sulfonamides.
• These findings have implications for predicting drug response and optimizing dosage based on acetylator phenotype.