EA 3620, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Br J Clin Pharmacol. 2012 Dec;74(6):971-7. doi: 10.1111/j.1365-2125.2012.04292.x.
This study was performed to describe clindamycin, administered either orally or intravenously, concentration-time courses to patients with osteomyelitis, to study the effects of different covariates on clindamycin pharmacokinetics and to simulate an optimized administration scheme.
Clindamycin concentrations were measured in 50 patients. A total of 122 plasma concentrations were available (58 from oral administration and 64 from i.v. infusion). A population pharmacokinetic model was developed with MONOLIX 4 software.
A one compartment model adequately described the data. Clindamycin clearance increased significantly with body weight (BW). The typical population estimates (interindividual variability) for clearance, volume of distribution and absorption rate constant were 16.2 l h(-1) (0.39), 70.2 l and 0.92 h(-1) , respectively. The bioavailability of the oral form was estimated to be 87.6%. According to BW, theoretical doses needed to reach a C(min) of 2 mg l(-1) were then calculated.
The current recommendation of 600 mg three times daily seems to be effective up to 75 kg but the dose should be raised to 900 mg three times daily thereafter. These assumptions should be prospectively confirmed.
本研究旨在描述给予骨髓炎患者口服或静脉注射克林霉素的浓度-时间曲线，研究不同协变量对克林霉素药代动力学的影响，并模拟优化的给药方案。
对 50 名患者进行克林霉素浓度检测。共获得 122 份血浆浓度数据（口服给药 58 份，静脉滴注 64 份）。采用 MONOLIX 4 软件建立群体药代动力学模型。
单室模型能很好地描述数据。克林霉素清除率随体重（BW）显著增加。清除率、分布容积和吸收速率常数的典型人群估计值（个体间变异性）分别为 16.2 l/h（0.39）、70.2 l 和 0.92/h。口服制剂的生物利用度估计为 87.6%。根据 BW，计算了达到 2mg/l（C(min)）所需的理论剂量。
目前推荐的 600mg 每日三次的剂量在体重不超过 75kg 时似乎有效，但此后应增加至 900mg 每日三次。这些假设应前瞻性地加以证实。
