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 of 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 ± 12.47 min to 62.96 ± 4.36 min (p < 0.001); AUC decreased from 10 617.38 ± 1179.81 μg 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⁻¹to 0.0068 ± 0.0007 L min⁻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.