A beneficial interaction between imipenem and piperacillin possibly through their renal excretory process.
In order to assess the beneficial mechanism of the concomitant use of imipenem (IPM) with piperacillin (PIPC) for the treatment of serious infectious diseases such as sepsis, the effects of PIPC on the uptake of IPM by rat renal cortical slices and on the plasma concentrations of IPM after intravenous infusion to rabbits were studied. The uptake of IPM by the rat renal cortical slices was significantly inhibited by p-aminohippurate, probenecid and PIPC whereas the uptake of PIPC by the slices was slightly decreased in the presence of IPM. When IPM was administered together with PIPC by 1-h infusion, the plasma concentrations of IPM were significantly increased during the infusion. These results imply that PIPC possibly interferes with the renal transport of IPM mediated by an organic anion transporter across the renal basolateral membranes, which leads to a longer period above the minimum inhibitory concentrations of IPM.
Saitoh
Hiroshi
H
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, and Department of Pharmacy, Health Sciences University of Hokkaido Hospital, Japan. saitoh@hoku-iryo-u.ac.jp
Oda
Masako
M
Gyotoku
Toru
T
Kobayashi
Michiya
M
Fujisaki
Hiroko
H
Sekikawa
Hitoshi
H
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D015378:Imipenem / Q000008:administration & dosage / Q000494:pharmacology* / Q000652:urine; D007668:Kidney / Q000502:physiology*; D010878:Piperacillin / Q000008:administration & dosage / Q000494:pharmacology* / Q000652:urine; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar
D015378:Imipenem; D010878:Piperacillin