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


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Doh
Kichan
K
Department of Pharmacology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, South Korea.
Woo
Heungjeong
H
Hur
Jun
J
Yim
Haejun
H
Kim
Jimyon
J
Chae
Hongseok
H
Han
Seunghoon
S
Yim
Dong-Seok
DS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001424:Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D002056:Burns / Q000150:complications*; D005260:Female; D006801:Humans; D007723:Korea; D008297:Male; D000077731:Meropenem; D008657:Metabolic Clearance Rate; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013845:Thienamycins / Q000008:administration & dosage* / Q000493:pharmacokinetics*
D000900:Anti-Bacterial Agents; D013845:Thienamycins; D000077731:Meropenem