Walstad R A, Dahl K, Hellum K B, Thurmann-Nielsen E
Department of Pharmacology and Toxicology, Faculty of Medicine, University of Trondheim, Norway.
Eur J Clin Pharmacol. 1988;35(3):273-9. doi: 10.1007/BF00558265.
We have studied the pharmacokinetics of ceftazidime in 37 patients suffering from serious bacterial infections. All the patients had impairment of renal function and received moderate to high doses of frusemide concurrently. The doses of ceftazidime were given according to renal function as recommended by the manufacturer. Serum and urine samples were frequently collected, and drug concentrations measured by high performance liquid chromatography. The patients were grouped and evaluated according to renal function, mean (SD) creatinine clearances ranging from 70.1 (12.4) to 11.0 (3.2) ml.min-1. The pharmacokinetics of ceftazidime depended on renal function. A statistically significant increase in ceftazidime elimination half-life and decreases in urinary recovery, total body clearance, and renal clearance in proportion to the decrease in renal function were observed (p less than 0.05). The apparent volume of distribution also increased, but not significantly (p greater than 0.05). A linear correlation was found between the total body and renal clearances of ceftazidime and creatinine clearance. The extrarenal clearance increased from 3.9 to 14.0 ml.min-1 with decreasing renal function. Concurrent treatment with ceftazidime and moderate to high doses of frusemide did not impair renal function and no evidence of nephrotoxicity was found.
我们研究了头孢他啶在37例严重细菌感染患者中的药代动力学。所有患者均存在肾功能损害，且同时接受了中到高剂量的呋塞米。头孢他啶的剂量按照生产商推荐根据肾功能给予。频繁采集血清和尿液样本，并用高效液相色谱法测定药物浓度。根据肾功能对患者进行分组和评估，平均（标准差）肌酐清除率范围为70.1（12.4）至11.0（3.2）ml·min⁻¹。头孢他啶的药代动力学取决于肾功能。观察到头孢他啶消除半衰期有统计学意义的增加，尿回收率、总体清除率和肾清除率随肾功能下降成比例降低（p<0.05）。表观分布容积也增加，但无统计学意义（p>0.05）。头孢他啶的总体清除率和肾清除率与肌酐清除率之间存在线性相关性。随着肾功能下降，肾外清除率从3.9增加至14.0 ml·min⁻¹。头孢他啶与中到高剂量呋塞米联合治疗未损害肾功能，也未发现肾毒性证据。
