Open AccessIntegration of pharmacokinetics and pharmacodynamics of imipenem in a human-adapted mouse model
Author(s) -
Ursula Flückiger,
C Segessenmann,
Andreas Gerber
Publication year - 1991
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.35.9.1905
Subject(s) - pharmacokinetics , imipenem , pharmacodynamics , pseudomonas aeruginosa , pharmacology , intramuscular injection , in vivo , escherichia coli , antibiotics , medicine , chemistry , microbiology and biotechnology , biology , anesthesia , bacteria , biochemistry , genetics , gene
The relationship between the pharmacokinetics and bactericidal activity of imipenem against Pseudomonas aeruginosa and Escherichia coli was investigated in a neutropenic mouse thigh infection model. To circumvent the problem of short elimination time in small animals, imipenem was administered in fractionized, decreasing doses such that the pharmacokinetic profiles as observed in humans after intravenous and intramuscular injections were approximated in mice. The human-simulated kinetic profile corresponding to an intramuscular injection of 500 mg at 12-h intervals proved to be as effective as the human-simulated profile of the same dose injected intravenously every 6 h. In contrast, the human-simulated profile corresponding to only one intravenous injection every 12 h resulted in bacterial breakthrough growth between 8 and 12 h after the onset of treatment. The results of our investigations confirm the hypothesis that the bactericidal effect of imipenem against P. aeruginosa and E. coli in vivo depends mainly on the time during which drug levels remain above the MIC rather than on the plasma peak/MIC ratio.