Kroh U F, Lennartz H, Edwards D J, Stoeckel K
Department of Anesthesiology and Intensive Therapy, Philipps University of Marburg, Germany.
J Clin Pharmacol. 1996 Dec;36(12):1114-9. doi: 10.1002/j.1552-4604.1996.tb04164.x.
Continuous hemofiltration is used widely in the management of patients with acute renal failure, but administration guidelines for many drugs have yet to be established. In this study, the pharmacokinetics of ceftriaxone were compared in patients with normal renal function (n = 9), mild renal insufficiency (n = 5), and acute renal failure receiving continuous veno-venous hemofiltration (n = 6). Pharmacokinetic parameters were determined under steady state conditions. Patients with mild renal insufficiency had a significantly lower renal clearance and longer half-life of ceftriaxone; however, drug recovery in the ultrafiltrate with continuous veno-venous hemofiltration was similar to that in the urine of patients with normal renal function. Pharmacokinetic parameters for renal, nonrenal, and systemic clearance and for volume of distribution and half-life were also similar between patients receiving continuous veno-venous hemofiltration and those with normal renal function. The sieving coefficient (S) of ceftriaxone (0.69) significantly exceeded the expected free fraction in plasma, confirming previous reports that protein binding does not limit the sieving of this compound. The results suggest that a reduction in the usual daily dose of ceftriaxone is not required in patients with acute renal failure receiving continuous veno-venous hemofiltration.
持续血液滤过在急性肾衰竭患者的治疗中被广泛应用,但许多药物的给药指南尚未确立。在本研究中,对肾功能正常的患者(n = 9)、轻度肾功能不全的患者(n = 5)和接受持续静-静脉血液滤过的急性肾衰竭患者(n = 6)的头孢曲松药代动力学进行了比较。在稳态条件下测定药代动力学参数。轻度肾功能不全的患者头孢曲松的肾清除率显著降低,半衰期延长;然而,持续静-静脉血液滤过患者超滤液中的药物回收率与肾功能正常患者尿液中的相似。接受持续静-静脉血液滤过的患者与肾功能正常的患者之间,肾清除率、非肾清除率、全身清除率以及分布容积和半衰期的药代动力学参数也相似。头孢曲松的筛过系数(S)为0.69,显著超过血浆中预期的游离分数,证实了先前关于蛋白质结合不限制该化合物筛过的报道。结果表明,接受持续静-静脉血液滤过的急性肾衰竭患者无需减少头孢曲松的常规日剂量。