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

✍ Scribed by Kuang-Yang Hsu; Dah-Jing Song; Yih Ho

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 572 KB
• Volume: 16
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/bdd.2510160308

✦ Synopsis

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 300mg kg-I, and an infusion rate of 7.5mgmin-I kg-' of PA, the concentration of PA reached a steady state (Cs,rlOOpgmL-l) in 30min. 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 p half-life, AUC, clearance, and klo of SDZ in slow acetylators: the f 3 half-life decreased from 11 5.74 f 12.47 min to 62.96*4.36min (p<O.OOl); AUC decreased from 10617.38* 1179.81 pgminmL-' to 6217.14* 391.32 pgminmL-' (p < 0.001); clearance increased from 0.0044 & 0.0008 Lmin-I kg-lto 0.0068 f 0.0007 Lmin-' kg-l(p < 0.001); and k,, increased from 0-0090 kO.0009min-' to 0.0193 *0.0028min-' (p <0.005). The reason for this may be that PA influences the elimination of SDZ in slow-acetylation rabbits.