Department of Hematology, First Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Pharmacy, First Affiliated Hospital of Harbin Medical University, Harbin, China.
J Clin Pharm Ther. 2022 Aug;47(8):1232-1239. doi: 10.1111/jcpt.13660. Epub 2022 Mar 28.
The aim of this study was to investigate the pharmacokinetics (PK) of cefoperazone (CFP) and sulbactam (SUL) in critically ill thrombotic thrombocytopenic purpura (TTP) patients undergoing therapeutic plasma exchange (TPE).
Critically ill TTP patients receiving a dose of 3 g CFP/SUL (2.0 g/1.0 g) intravenously every 8 h were included in the study. TPE session began 10 min after the end of CFP/SUL infusion. Serial blood samples were collected at 0, 1, 2, 3, 4, 6 and 8 h at the fourth infusion with TPE and the sixth infusion without TPE. Effluent samples were collected at the effluent port of plasma eliminated at the end of TPE. Concentrations of CFP and SUL in plasma and effluent were measured using LC-MS/MS. PK parameters were calculated based on two-compartment open model.
Five critically ill TTP patients receiving CFP/SUL monotherapy were enrolled. T of CFP and SUL with TPE was 0.62 and 1.30 h, respectively. For CFP, T with TPE were significantly higher than those without TPE (5.85 ± 3.16 vs. 4.41 ± 2.74, p = 0.016). V with TPE were significantly higher than those without TPE (7.23 ± 0.89 vs. 5.24 ± 0.80 L, p = 0.024). AUC with TPE were significantly lower compared with those without TPE (1380.98 ± 411.99 vs. 1581.61 ± 500.22 mg*h/L, p = 0.011). Relatively, CL with TPE were significantly higher than those without TPE (1.56 ± 0.46 vs. 1.37 ± 0.44 L/h, p = 0.010). For SUL, V and CL were higher significantly with TPE than those without TPE (28.11 ± 8.42 vs. 18.87 ± 6.45 L, p = 0.002; 10.74 ± 2.01 vs. 8.60 ± 2.10 L/h, p = 0.048). Mean Q of CFP and SUL were 344.42 ± 55.37 and 34.65 ± 10.09 mg, respectively. Mean fe% of CFP and SUL were 17.22 ± 2.77% and 3.46 ± 1.01%, respectively.
TPE enhances the clearance of CFP and SUL in critically ill TTP patients. CFP is more likely to be removed than SUL due to its a low V and high Pb. TPE is suggested to begin 1-2 h after the end of CFP/SUL infusion. Plasma concentration monitoring is advised when CFP/SUL must be administered during TPE.
本研究旨在探讨接受治疗性血浆置换（TPE）的危重症血栓性血小板减少性紫癜（TTP）患者中头孢哌酮（CFP）和舒巴坦（SUL）的药代动力学（PK）。
本研究纳入了接受 3 g CFP/SUL（2.0 g/1.0 g）每 8 小时静脉注射的危重症 TTP 患者。TPE 疗程在 CFP/SUL 输注结束后 10 分钟开始。在第四次输注 TPE 和第六次输注无 TPE 时，分别在 0、1、2、3、4、6 和 8 小时采集血样。在 TPE 结束时从血浆消除的出口端收集流出样本。采用 LC-MS/MS 法测定血浆和流出液中 CFP 和 SUL 的浓度。根据两室开放模型计算 PK 参数。
本研究纳入了 5 名接受 CFP/SUL 单药治疗的危重症 TTP 患者。TPE 下 CFP 和 SUL 的 T 分别为 0.62 和 1.30 h。对于 CFP，TPE 下的 T 明显高于无 TPE 时的 T（5.85±3.16 比 4.41±2.74，p=0.016）。TPE 下的 V 明显高于无 TPE 时的 V（7.23±0.89 比 5.24±0.80 L，p=0.024）。TPE 下的 AUC 明显低于无 TPE 时的 AUC（1380.98±411.99 比 1581.61±500.22 mg*h/L，p=0.011）。相对地，TPE 下的 CL 明显高于无 TPE 时的 CL（1.56±0.46 比 1.37±0.44 L/h，p=0.010）。对于 SUL，TPE 下的 V 和 CL 明显高于无 TPE 时的 V 和 CL（28.11±8.42 比 18.87±6.45 L，p=0.002；10.74±2.01 比 8.60±2.10 L/h，p=0.048）。CFP 和 SUL 的平均 Q 分别为 344.42±55.37 和 34.65±10.09 mg。CFP 和 SUL 的平均 fe%分别为 17.22±2.77%和 3.46±1.01%。
TPE 增强了危重症 TTP 患者中 CFP 和 SUL 的清除率。由于 CFP 的 V 较低而 Pb 较高，因此 CFP 比 SUL 更有可能被清除。建议在 CFP/SUL 输注结束后 1-2 小时开始 TPE。当必须在 TPE 期间给予 CFP/SUL 时，建议进行血浆浓度监测。
