Isla Arantxazu, Maynar Javier, Sánchez-Izquierdo José Angel, Gascón Alicia R, Arzuaga Alazne, Corral Esther, Pedraz José Luis
Laboratory of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of the Basque Country, Vitoria-Gasteiz, Spain.
J Clin Pharmacol. 2005 Nov;45(11):1294-304. doi: 10.1177/0091270005280583.
The pharmacokinetics of meropenem were characterized in 20 patients with different degrees of renal function who underwent continuous renal replacement therapy. Previously, no differences were detected in vitro in the removal of meropenem by continuous venovenous hemofiltration or continuous venovenous hemodialysis or when AN69 or polysulfone membranes were compared. In patients, no significant differences in the sieving coefficient or the saturation coefficient with the renal function were found, and the mean sieving coefficient/saturation coefficient value (0.80 +/- 0.12) was similar to the unbound fraction (0.79 +/- 0.08). An increase in total clearance and a decrease in elimination half-life were observed to the extent that the patient's creatinine clearance was higher. Likewise, the contribution of continuous renal replacement therapy to total clearance diminished in patients with less renal impairment. The results suggest that the renal function of the patient may influence meropenem pharmacokinetics during continuous renal replacement therapy. The lower trough plasma levels observed in nonrenal patients would not lead to adequate time during which serum drug concentrations are above the minimum inhibitory concentration values in many infections.
对20例接受持续肾脏替代治疗且肾功能程度不同的患者进行了美罗培南的药代动力学研究。此前，在体外比较持续静静脉血液滤过或持续静静脉血液透析对美罗培南的清除情况，以及比较AN69或聚砜膜时，未发现差异。在患者中，未发现筛过系数或饱和系数随肾功能有显著差异，平均筛过系数/饱和系数值（0.80±0.12）与游离分数（0.79±0.08）相似。观察到患者的肌酐清除率越高，总清除率增加且消除半衰期缩短。同样，在肾功能损害较轻的患者中，持续肾脏替代治疗对总清除率的贡献减小。结果表明，在持续肾脏替代治疗期间，患者的肾功能可能会影响美罗培南的药代动力学。在非肾脏疾病患者中观察到的较低血浆谷浓度，在许多感染中不会产生足够长的时间使血清药物浓度高于最低抑菌浓度值。
