Walstad R A, Aanderud L, Thurmann-Nielsen E
Department of Pharmacology and Toxicology, University of Trondheim, Norway.
Eur J Clin Pharmacol. 1988;35(5):543-9. doi: 10.1007/BF00558251.
The pharmacokinetics and tissue concentrations of ceftazidime have been investigated in 8 patients with severe burns (20-80% of body surface area) undergoing skin transplantation 2 to 21 days after injury. Two prophylactic doses of ceftazidime were administered as 1 g i.v. bolus injections with an 8 h interval. Blood, urine, burn blister fluid and tissue were frequently sampled and drug concentrations were analyzed by HPLC. The kinetics of ceftazidime was the same after each dose. In these patients the pharmacokinetics of ceftazidime was greatly altered from that in other patients and there was much interindividual variation. The mean ceftazidime elimination half-life, apparent volume of distribution and total clearance were: 2.7 h, 30.91 (0.38 1.kg-1) and 139 ml.min-1, respectively. A linear correlation was found between creatinine clearance and the renal clearance of the ceftazidime, the mean values being 108 and 95 ml.min-1, respectively. No correlation was found between creatinine clearance and the total clearance of ceftazidime. The mean percentage urine recovery was 69% of the dose. Tissue and burn blister fluid concentrations were above the MIC, and ranged from 40.0 to 3.1 mg.kg-1. A substantial increase in the apparent volume of distribution and non-renal clearance of ceftazidime was observed, probably due to increased capillary permeability and drug loss through the wound surface replacement of prior to surgery and subsequently to lost and blood fluid.
对8例严重烧伤（体表面积20%-80%）患者在受伤后2至21天接受皮肤移植手术期间头孢他啶的药代动力学和组织浓度进行了研究。给予两次预防性剂量的头孢他啶，每次1g静脉推注，间隔8小时。频繁采集血液、尿液、烧伤水泡液和组织样本，采用高效液相色谱法分析药物浓度。每次给药后头孢他啶的动力学相同。在这些患者中，头孢他啶的药代动力学与其他患者相比有很大改变，个体间差异很大。头孢他啶的平均消除半衰期、表观分布容积和总清除率分别为：2.7小时、30.91（0.38L·kg⁻¹）和139ml·min⁻¹。肌酐清除率与头孢他啶的肾清除率之间存在线性相关性，平均值分别为108和95ml·min⁻¹。未发现肌酐清除率与头孢他啶的总清除率之间存在相关性。尿回收率的平均值为给药剂量的69%。组织和烧伤水泡液浓度高于最低抑菌浓度，范围为40.0至3.1mg·kg⁻¹。观察到头孢他啶的表观分布容积和非肾清除率大幅增加，可能是由于毛细血管通透性增加以及手术前伤口表面置换导致的药物损失，以及随后体液丢失和失血所致。
