Rohde B, Werner U, Hickstein H, Ehmcke H, Drewelow B
Department of Clinical Pharmacology, University of Rostock, Germany.
Eur J Clin Pharmacol. 1997;53(2):111-5. doi: 10.1007/s002280050347.
In intensive care medicine, continuous detoxication methods, such as continuous veno-venous hemodialysis (CVVHD), are used for treating acute renal failure. However, in contrast to conventional hemodialysis, little is known about the pharmacokinetics of many drugs administered in this setting and guidelines for dosages of drugs often do not exist. This holds particularly true for broad-spectrum antibiotics, which are often required during intensive care.
In this study, we investigated the pharmacokinetics of the acylureidopenicillin mezlocillin and the beta-lactamase inhibitor sulbactam during CVVHD and deduced dosage recommendations from the kinetic parameters with the goal of maintaining trough levels of above 10 mg.l-1 for mezlocillin and 5 mg.l-1 for sulbactam. Six intensive care patients with acute renal failure, receiving mezlocillin (n = 5) and/or sulbactam (n = 4), were examined during CVVHD and during intervals between CVVHD. The serum concentrations and the amounts of the drugs excreted into the dialyzate and into the urine within one dosage interval were measured using high performance liquid chromatography (HPLC). Three of the patients were jaundiced, indicating functional impairment of the liver.
The clearances by CVVHD (CLCVVHD) for mezlocillin ranged between 11.0 and 44.9 ml.min-1 and the half lives ranged between 1.12 and 8.84 h. Low CL and long half lives were observed in the patients with jaundice. For sulbactam, CLCVVHD ranged between 10.1 and 22.8 ml.min-1 and serum half lives were 4.25-6.11 h, independent of liver function.
Due to high hepatobiliary clearance of mezlocillin, dosage adjustments in patients with acute renal failure, treated by CVVHD, are needed only with concurrent impaired liver function. For sulbactam, the optimal dose was found to be 0.5 g, administered every 12 h, regardless of liver function.
在重症监护医学中，持续解毒方法，如持续静静脉血液透析（CVVHD），用于治疗急性肾衰竭。然而，与传统血液透析不同，在此情况下使用的许多药物的药代动力学鲜为人知，且通常不存在药物剂量指南。对于重症监护期间经常需要使用的广谱抗生素而言尤其如此。
在本研究中，我们调查了美洛西林（一种酰脲类青霉素）和β-内酰胺酶抑制剂舒巴坦在CVVHD期间的药代动力学，并根据动力学参数推导剂量建议，目标是使美洛西林的谷浓度维持在10mg·l-1以上，舒巴坦的谷浓度维持在5mg·l-1以上。对6例接受美洛西林（n = 5）和/或舒巴坦（n = 4）治疗的急性肾衰竭重症监护患者在CVVHD期间及CVVHD间隔期进行了检查。使用高效液相色谱法（HPLC）测量了一个给药间隔期内血清浓度以及排泄到透析液和尿液中的药物量。其中3例患者有黄疸，提示肝功能受损。
美洛西林的CVVHD清除率（CLCVVHD）在11.0至44.9ml·min-1之间，半衰期在1.12至8.84小时之间。黄疸患者观察到清除率低和半衰期长。对于舒巴坦，CLCVVHD在10.1至22.8ml·min-1之间，血清半衰期为4.25 - 6.11小时，与肝功能无关。
由于美洛西林的肝胆清除率高，在接受CVVHD治疗的急性肾衰竭患者中，仅在同时存在肝功能受损时才需要调整剂量。对于舒巴坦，发现最佳剂量为0.5g，每12小时给药一次，与肝功能无关。
