Clinical Pharmacokinetics Unit, Division of Intensive Care and Emergency Medicine, Department of Internal Medicine I, Medical University of Innsbruck, Innsbruck, Austria.
Department of Clinical Pharmacy, Institute of Pharmacy, University of Hamburg, Hamburg, Germany.
J Antimicrob Chemother. 2020 May 1;75(5):1237-1241. doi: 10.1093/jac/dkz556.
We investigated the effect of continuous renal replacement therapy (CRRT) on the pharmacokinetics of trimethoprim and sulfametrole.
We enrolled critically ill adults undergoing CRRT and critically ill adults with normal or slightly impaired renal function (plasma creatinine concentration <1.5 mg/dL, control group). All patients received trimethoprim/sulfametrole at standard doses. Pharmacokinetics were determined after the first dose and at steady-state. In addition, a population pharmacokinetic model using plasma data was built. We also assessed the renal clearance (CLR) and the extracorporeal clearance in patients undergoing CRRT.
Twelve patients were enrolled in the CRRT group and 12 patients in the control group. There was no statistically significant difference in trimethoprim pharmacokinetics between the two groups. In patients on CRRT, total plasma clearance (CLtot) and V of sulfametrole were significantly higher than in the control group. However, sulfametrole exposure was not significantly altered during CRRT. The population pharmacokinetic analysis indicated that neither CRRT intensity nor residual diuresis were significant covariates on trimethoprim or sulfametrole CL. Median CL by continuous venovenous haemofiltration accounted for about one-third of CLtot of trimethoprim and for about one-half of CLtot of sulfametrole. In patients on CRRT, CLR of trimethoprim and sulfametrole were <5% of CLtot.
During CRRT, standard doses of trimethoprim/sulfametrole appear to be adequate.
我们研究了连续肾脏替代疗法（CRRT）对甲氧苄啶和磺胺甲恶唑药代动力学的影响。
我们纳入正在接受 CRRT 的重症患者和肾功能正常或轻度受损的重症患者（血浆肌酐浓度＜1.5mg/dL，对照组）。所有患者均接受标准剂量的甲氧苄啶/磺胺甲恶唑治疗。在首剂后和稳态时测定药代动力学。此外，我们还使用血浆数据构建了群体药代动力学模型。我们还评估了正在接受 CRRT 的患者的肾清除率（CLR）和体外清除率。
12 例患者纳入 CRRT 组，12 例患者纳入对照组。两组患者的甲氧苄啶药代动力学无统计学差异。在接受 CRRT 的患者中，磺胺甲恶唑的总血浆清除率（CLtot）和 V 显著高于对照组。然而，CRRT 期间磺胺甲恶唑的暴露并未显著改变。群体药代动力学分析表明，CRRT 强度和残余尿量均不是甲氧苄啶和磺胺甲恶唑 CL 的显著协变量。连续静脉-静脉血液滤过的群体药代动力学分析表明，CLtot 中约有三分之一是甲氧苄啶的 CL，约有一半是磺胺甲恶唑的 CL。在接受 CRRT 的患者中，甲氧苄啶和磺胺甲恶唑的 CLR ＜5%的 CLtot。
在 CRRT 期间，甲氧苄啶/磺胺甲恶唑的标准剂量似乎是足够的。
