Pharmacokinetics and tissue concentrations of ceftazidime in burn patients

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.