During the past few years, acetylation polymorphism has been shown to be a proven, established fact, and N-acetyltransferase, an enzyme that transfers an acetyl group to the substrate, has been recognized as the main factor in acetylation polymorphism. In a recent study, a significant difference between the acetylation phenotype and plasma pyruvic acid (PA) concentration in rabbits was found. In this report, the influence of PA on the pharmacokinetics of sulphadiazine (SDZ), a drug that has been used in pharmacogenetic studies of acetylation, was studied. By using a loading dose of 300 mg kg-1, and an infusion rate of 7·5 mg min-1 kg-1 of PA, the concentration of PA reached a steady state (C(ss)≃ 100 μg mL-1) in 30 min. During PA infusion in rapid-acetylation rabbits, no significant changes were found in any of the pharmacokinetic parameters for SDZ. However, differences were found in the β half-life, AUC, clearance, and k10 of SDZ in slow acetylators: the β half-life decreased from 115.74 ± 12.47min to 62.96 ± 4.36 min (p <0.001); AUC decreased from 10617.38 ± 1179.81 μg min mL-1 to 6217.14 ± 391.32 μg min mL-1 (p <0.001); clearance increased from 0.0044 ± 0.0008 Lmin-1 kg-1 to 0.0068 ± 0.0007 Lmin-1 kg-1 (p <0.001); and k10 increased from 0.0090 ± 0.0009 min-1 to 0.0193 ± 0.0028 min-1 (p <0.005). The reason for this may be that PA influences the elimination of SDZ in slow-acetylation rabbits.
ASJC Scopus subject areas
- 藥理學、毒理學和藥劑學 (全部)