Facility for Anti-infective Drug Development and Innovation, Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Victoria, Australia.
J Antimicrob Chemother. 2009 Nov;64(5):1067-70. doi: 10.1093/jac/dkp331. Epub 2009 Sep 10.
To determine the disposition of novel antimicrobial cationic peptides NAB 7061 and NAB 739 following intravenous administration in rats.
Sprague-Dawley rats received a single intravenous bolus of 1.0 mg/kg NAB 7061 or NAB 739. Plasma concentrations of NAB 7061 or NAB 739 were determined by HPLC or liquid chromatography-mass spectrometry. The pharmacokinetic parameters of NAB 7061 and NAB 739 were calculated using non-compartmental analysis.
Corresponding total body clearance, volume of distribution at steady state and terminal half-life of NAB 7061 and NAB 739 averaged 3.84 and 2.63 mL/min/kg, 339 and 222 mL/kg, and 66.2 and 69.0 min, respectively. Approximately 7.16% and 19.4% of the dose was eliminated in an unchanged form via the urine in 24 h for NAB 7061 and NAB 739, respectively.
While both compounds had generally similar pharmacokinetics to colistin, even minor alterations in the chemical structures appear to have an impact on their pharmacokinetics, especially on their clearance by the kidney. There are also substantial differences in relation to the relative contributions of renal and non-renal clearance to overall elimination from the body.
确定新型抗菌阳离子肽 NAB 7061 和 NAB 739 静脉给药后在大鼠体内的处置情况。
Sprague-Dawley 大鼠单次静脉推注 1.0 mg/kg NAB 7061 或 NAB 739。通过 HPLC 或液质联用测定 NAB 7061 或 NAB 739 的血浆浓度。采用非房室分析计算 NAB 7061 和 NAB 739 的药代动力学参数。
NAB 7061 和 NAB 739 的相应总清除率、稳态分布容积和终末半衰期分别平均为 3.84 和 2.63 mL/min/kg、339 和 222 mL/kg 以及 66.2 和 69.0 min。NAB 7061 和 NAB 739 在 24 小时内以未改变的形式通过尿液分别消除约 7.16%和 19.4%的剂量。
虽然这两种化合物的药代动力学与粘菌素大致相似，但即使是化学结构的微小改变似乎也会影响它们的药代动力学特性，尤其是它们的肾脏清除率。此外，肾脏和非肾脏清除率对总体消除的相对贡献也存在显著差异。
