ABSTRACT
The aims of this study were to evaluate pharmacokinetic (PK) parameters of total and unbound ertapenem (ERT) in burns patients and to identify which covariates influence these PK parameters. ERT plasma concentrations were measured in burns patients (n = 8) who received a 0.5-h infusion of ERT (1000 mg) every 24 h. PK parameters were estimated by a non-compartmental approach and the influence of covariates was estimated by multivariate analysis using a population approach. Clearance (CL) and the volume of distribution (V) of total ERT were lower than the results for unbound ERT [CL, 22.2 ± 5.6 mL/min vs. 279.4 ± 208.2 mL/min; V, 9.7 ± 1.4L vs. 120.6 ± 130.6L (mean ± standard deviation)]. Creatinine clearance (CL(Cr)) and the burned surface area (BSA) were the covariates identified that significantly (P<0.01) affected the pharmacokinetics of total ERT [CL (L/h)=0.373 +{0.00666 x CL(Cr) (mL/min)}] and unbound ERT [peripheral volume of distribution (L) = 3.05 + {0.959 x BSA (% of the total body surface)}], respectively. The influences of albuminaemia, glomerular filtration and burn wound on ERT pharmacokinetics are proposed to explain these results. These first results support that the ERT plasma concentration should be closely monitored particularly for patients with high values of BSA and/or CL(Cr) to avoid suboptimal exposure.
