Pharmacokinetics and pharmacodynamic assessment of imipenem in the intraperitoneal fluid of abdominal surgery patients.
BACKGROUND
Imipenem is used to treat intra-abdominal infections, however, this treatment would benefit from a better understanding of imipenem penetration into the abdominal cavity.


METHODS
Imipenem 500 mg was infused to 10 laparotomy patients. The total drug concentrations in plasma and intraperitoneal fluid were analyzed noncompartmentally and 3-compartmentally (population pharmacokinetic analysis), and used for a Monte Carlo simulation with minimum inhibitory concentration data.


RESULTS
The AUC(0-infinity) ratio of the intraperitoneal fluid to the plasma was 0.82 +/- 0.06 (mean +/- SD, n = 6). The pharmacodynamic exposures in the intraperitoneal fluid were higher than in the plasma. The probabilities of achieving a bacteriostatic/bactericidal target (20/40% of the time above minimum inhibitory concentration for 24 h) in the intraperitoneal fluid using a regimen of 500 mg every 8 h against the Bacteroides fragilis group, Escherichia coli and Klebsiella species were 97.3/89.1, 98.8/97.2 and 100/98.2%, respectively. However, a regimen of 1,000 mg every 8 h was needed to achieve 96.7/89.3% against Pseudomonas aeruginosa.


CONCLUSIONS
These results may help us to understand the intraperitoneal penetration of imipenem and to determine the dosing regimen for intra-abdominal infections.
Ikawa
Kazuro
K
Department of Clinical Pharmacotherapy, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. ikawak@hiroshima-u.ac.jp
Morikawa
Norifumi
N
Sakamoto
Kenichi
K
Ikeda
Kayo
K
Ohge
Hiroki
H
Takesue
Yoshio
Y
Sueda
Taijiro
T
D000328:Adult; D000368:Aged; D001202:Ascitic Fluid / Q000187:drug effects* / Q000378:metabolism* / Q000382:microbiology; D013505:Digestive System Surgical Procedures / Q000379:methods; D005260:Female; D006801:Humans; D015378:Imipenem / Q000097:blood* / Q000494:pharmacology*; D007263:Infusions, Parenteral; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D008875:Middle Aged
D015378:Imipenem