Metabolic kinetics of p-aminobenzoic acid in rabbits

The metabolic kinetics of p-aminobenzoic acid (PABA) in rabbits was studied . PABA is predominantly metabolized by acetylation and glycine conjugation to form p-acetamidobenzoic acid (PAABA), p-aminohippuric acid (PAHA), and p -acetamidohippuric acid (PAAHA). After PABA TV administration (20 mg/kg) to rapid (n = 16) and slow (n = 8) acetylation rabbits, PABA was eliminated r apidly. The half-lives of PABA were 7.01 +/- 0.32 min in rapid acetylation rabbits and 7.08 +/- 0.78 min in slow acetylation rabbits. Significant diff erences were obtained in formation of PAABA and PAHA formed from PABA in bo th acetylation phenotype rabbits. The formation fraction of PAABA, formed b y acetylation of PABA, was 0.8029 +/- 0.0267 in rapid acetylators and 0.238 5 +/- 0.0428 in slow acetylators (p < 0.001). PAHA formed from PABA was 0.0 462 +/- 0.0102 in rapid acetylators and 0.6652 +/- 0.0562 in slow acetylato rs (p < 0.001). Only 0.0156 +/- 0.0030 of PABA could be detected as PAAHA i n rapid acetylation rabbits which was obtained by acetylation of PAHA. Afte r individual IV injection of PAHA, PAAHA, and PAABA to both phenotypes of r abbits, PAABA and PAAHA were eliminated in their unchanged forms whereas PA HA was further acetylated to form PAAHA. The formation fraction of PAAHA fo rmed from the acetylation of PAHA was 0.4408 +/- 0.0570 in rapid acetylator s and 0.0539 +/- 0.0084 in slow acetylators (p = 0.002). From the results o btained, metabolic pathways of PABA show significant differences in both ac etylation phenotypes of rabbits. Acetylation is the major metabolic route o f PABA in rapid acetylation rabbits, while glycine conjugation is more pred ominant in slow acetylation rabbits. Copyright (C) 1999 John Wiley & Sons, Ltd.