Population pharmacokinetics of meropenem in febrile neutropenic patients in Korea

• Published in: International journal of antimicrobial agents 2006-10, Vol.28 (4), p.333-339
• Main Authors: Lee, Dong-Gun, Choi, Su-Mi, Shin, Wan-Shik, Lah, Hyon-Oh, Yim, Dong-Seok
• Format: Article
• Language: English
• Subjects: Adult; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacokinetics; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Creatinine - blood; Dose-Response Relationship, Drug; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli - drug effects; Escherichia coli - isolation & purification; Fever - metabolism; Hematologic and hematopoietic diseases; Humans; Korea; Medical sciences; Meropenem; MIC; Microbial Sensitivity Tests; Models, Biological; Neutropenia; Neutropenia - metabolism; Other diseases. Hematologic involvement in other diseases; Pharmacology. Drug treatments; Population; Population pharmacokinetics; Pseudomonas aeruginosa; Pseudomonas aeruginosa - drug effects; Pseudomonas aeruginosa - isolation & purification; Simulation; Thienamycins - pharmacokinetics; Thienamycins - pharmacology
• ISSN: 0924-8579; 1872-7913
• DOI: 10.1016/j.ijantimicag.2006.05.033

Population pharmacokinetic parameters of meropenem in 57 febrile neutropenic patients and minimal inhibitory concentration (MIC) data for clinically isolated Pseudomonas aeruginosa and Escherichia coli were applied to estimate the time above the MIC ( T > MIC) using the Monte Carlo simulation method. Mean population clearance (CL) and volume of distribution ( V d) of meropenem were proportional to creatinine clearance (CL Cr) and body weight, respectively: CL (L/h) = 9.7 × (CL Cr (mL/min)/120); V d (L) = 14.6 × (body weight (kg)/61). In 1000 simulated patients treated with meropenem 0.5 g or 1 g every 8 h, the proportions of patients who had a T > MIC less than 40% of the dosing interval were 46.3% and 39.5% for P. aeruginosa and 5.8% and 5.6% for E. coli, respectively. The overwhelming resistance of the pathogenic microorganisms, especially P. aeruginosa, in our data compared with that reported in North America suggests the importance of regions or countries as a critical factor for determining the dosage regimen of meropenem in addition to patient characteristics and pharmacokinetics.