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The influence of pyruvic acid on the pharmacokinetics of sulphadiazine in rabbits
Author(s) -
Hsu KuangYang,
Song DahJing,
Ho Yih
Publication year - 1995
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2510160308
Subject(s) - pharmacokinetics , chemistry , acetylation , pharmacology , volume of distribution , biochemistry , medicine , gene
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 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 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 −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 ( p < 0.005). The reason for this may be that PA influences the elimination of SDZ in slow‐acetylation rabbits.