Population pharmacokinetics of meropenem in burn patients

To develop a population pharmacokinetic model of meropenem in burn patients and to explore the appropriateness of current dosage regimens.

Fifty-nine patients with burns ranging from 3% to 97% of total body surface area treated with meropenem were analysed. The population pharmacokinetic parameters of meropenem in 59 burn patients were estimated, and concentrations were simulated by using a mixed effect method (NONMEM, ver. 6.2).

The final model was a two-compartment model with first-order elimination where creatinine clearance (CL(CR)) and oedema contributed. The mean population pharmacokinetic parameters were clearance (L/h) =4.45 +10.5 × CL(CR) (mL/min)/138, V1 (central volume) =17.0+11.1 × presence of oedema (0 or 1) L, V2 (peripheral volume) =10.1 L and Q (intercompartmental clearance) =5.25 L/h with interindividual variability (CV%) of 31.5%, 44.4%, 67.2% and 0% (not estimated), respectively.

The population clearance and volume of distribution in our burn patients were significantly greater than those reported in non-burn patients. The simulation of 1000 virtual patients' plasma meropenem concentration treated with 1000 mg (30 min infusion) every 8 h based upon the model predicted the probability of achieving the time above MIC >40% of the dosing interval as 58.9% for Pseudomonas aeruginosa isolated from three university hospitals in Korea.