Peritoneal penetration of doripenem after intravenous administration in abdominal-surgery patients.
OBJECTIVE
This study aimed to examine the peritoneal penetration of intravenous doripenem, a novel carbapenem used for the treatment of intra-abdominal infections.


METHODS
Doripenem (500 mg) was administered to 10 patients before abdominal surgery. Venous blood and peritoneal exudate samples were obtained at the end of infusion (0.5 h) and every hour for 6 h afterwards. The drug concentrations in serum and exudate were measured using HPLC, estimated by non-compartmental pharmacokinetic analysis and fitted to a three-compartment pharmacokinetic model in order to assess the exposure time that the drug concentration remained above MIC.


RESULTS
The AUC(0-infinity) was 59.3 +/- 7.2 mg.h/L (mean +/- SD) in serum and 49.3 +/- 6.5 mg.h/L in exudate, and the exudate/serum ratio was 0.84 +/- 0.13. The observed maximum concentration was 46.9 +/- 7.4 mg/L at 0.5 h in serum and 24.5 +/- 6.5 mg/L at 0.7 +/- 0.4 h in exudate, and the exudate/serum ratio was 0.53 +/- 0.17. The compartmental analysis showed that the average concentrations remained higher in exudate than in serum after 0.81 h post-dose, and the average drug-exposure times in serum (91% fraction unbound) and exudate were: 73.6% and 78.2% at an MIC of 1 mg/L; 37.0% and 41.5% at 4 mg/L; and 12.7% and 13.1% at 16 mg/L.


CONCLUSIONS
Following intravenous administration, doripenem penetrated well into peritoneal exudate of abdominal-surgery patients, and the drug-exposure times in exudate were greater than or equal to those estimated from serum data.
Ikawa
Kazuro
K
Department of Clinical Pharmacotherapy, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. ikawak@hiroshima-u.ac.jp
Morikawa
Norifumi
N
Urakawa
Nami
N
Ikeda
Kayo
K
Ohge
Hiroki
H
Sueda
Taijiro
T
D000005:Abdomen / Q000601:surgery*; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019540:Area Under Curve; D015780:Carbapenems / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000077726:Doripenem; D005122:Exudates and Transudates / Q000378:metabolism*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D010537:Peritoneum / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D000077726:Doripenem