title: The influence of pyruvic acid on the pharmacokinetics of sulphadiazine in rabbits.
abstract: 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 (Css approximately equal to 100 micrograms 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 beta half-life, AUC, clearance, and k10 of SDZ in slow acetylators: the beta 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 micrograms min mL-1 to 6217.14 +/- 391.32 micrograms 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 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.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Taipei Medical Collegé, Taiwan.
authors.forename: K Y
authors.initials: KY
authors.lastname: Hsu
authors.forename: D J
authors.initials: DJ
authors.lastname: Song
authors.forename: Y
authors.initials: Y
authors.lastname: Ho
mesh_terms: D000107:Acetylation; D000818:Animals; D004347:Drug Interactions; D007262:Infusions, Intravenous; D008297:Male; D010641:Phenotype; D011773:Pyruvates / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D019289:Pyruvic Acid; D011817:Rabbits; D013411:Sulfadiazine / Q000493:pharmacokinetics*
chemical_list: D011773:Pyruvates; D013411:Sulfadiazine; D019289:Pyruvic Acid