Van Wart S A, Cirincione B B, Ludwig E A, Meagher A K, Korth-Bradley J M, Owen J S
Cognigen Corporation, 395 Youngs Road, Buffalo, NY 14221, USA.
J Clin Pharmacol. 2007 Jun;47(6):727-37. doi: 10.1177/0091270007300263.
Tigecycline, a novel glycylcycline, possesses broad-spectrum antimicrobial activity. A structural population pharmacokinetic model for tigecycline was developed based on data pooled from 5 phase I studies. Intravenous tigecycline was administered as single (12.5-300 mg) or multiple (25-100 mg) doses every 12 hours for up to 10 days. Three-compartment models with zero-order input and first-order elimination separately described the single- or multiple-dose full-profile data. Additional models were evaluated using a subset of the phase I data mimicking the phase II/III trial sparse-sampling scheme and dosage. A 2-compartment model best described the reduced phase I data following single or multiple doses and provided reliably accurate estimates of tigecycline AUC(0-12). This modeling supported phase II/III population pharmacokinetic model development to further determine individual patient tigecycline exposures for safety and efficacy analyses.
替加环素是一种新型甘氨酰环素，具有广谱抗菌活性。基于5项I期研究汇总的数据，建立了替加环素的结构群体药代动力学模型。静脉注射替加环素，每12小时给予单剂量（12.5 - 300毫克）或多剂量（25 - 100毫克），持续给药长达10天。具有零级输入和一级消除的三室模型分别描述了单剂量或多剂量的全谱数据。使用模拟II/III期试验稀疏采样方案和剂量的I期数据子集评估了其他模型。两室模型最能描述单剂量或多剂量后减少的I期数据，并能可靠准确地估计替加环素的AUC(0 - 12)。该模型为II/III期群体药代动力学模型的开发提供了支持，以进一步确定个体患者的替加环素暴露量，用于安全性和疗效分析。
