The influence of pyruvic acid on the pharmacokinetics of sulphadiazine in rabbits

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 rapidacetylation 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 k 10 of SDZ in slow acetylators: the β half-life decreased from 115.74±12.47 min 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 L min -1 kg -1 to 0.0068±0.0007 L min -1 kg -1 (p<0.001); AND K 10 increased from 0.0090±0.0009 min -1 to 0.0193±0.0028 min -1 kg -1 (p<0.005). The reason for this may be that PA influences the elimination of SDZ in slow-acetylation rabbits