Peritoneal transport of β‐lactam antibiotics: Effects of plasma protein binding and the interspecies relationship

Yoshiharu Deguchi, Emi Nakashima, Fusashi Ishikawa, Hitoshi Sato, Ikumi Tamai, Ryo Matsushita, Yohei Tofuku, Fujio Ichimura, Akira Tsuji

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Abstract

In order to examine quantitatively the effect of plasma protein binding on the peritoneal transport of β‐lactam antibiotics, we employed a kinetic model based on the pore theory of transcapillary exchange. This model incorporates the changes in the volume, osmolality, and antibiotic concentration in the dialysate, so that the apparent capillary membrane permeability (Pd) and the reflection coefficient (s̀d) of an antibiotic could be assessed. Six cephalosporins (cefatrizine, cefazolin, cefpiramide, ceftazidime, ceftriaxone, cephaloridine) were used as model compounds. While the unbound fractions of these antibiotics ranged widely from 0.08 to 0.57, including linear and nonlinear protein binding, the concentration–time profiles in plasma and the peritoneal dialysate after intravenous administration in rats could be interpreted well by our model, assuming that only the unbound antibiotic is available for the peritoneal transport. The estimated Pd values were almost the same among the drugs examined. Moreover, the Pd values of cefazolin in mice, rats, and rabbits exhibited a 0.83‐power dependency on the animal body weight, indicating that Pd is significantly related to the peritoneal surface area. On the other hand, the s̀d values of cefazolin were found to be almost the same among the animal species examined. Finally, the concentration–time profile of cefazolin in the dialysate after intravenous administration in a patient with end‐stage renal failure was successfully predicted using the Pd value extrapolated from those of the experimental animals.

Original languageEnglish
Pages (from-to)559-564
Number of pages6
JournalJournal of Pharmaceutical Sciences
Volume77
Issue number7
DOIs
Publication statusPublished - 1988 Jul

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ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Deguchi, Y., Nakashima, E., Ishikawa, F., Sato, H., Tamai, I., Matsushita, R., Tofuku, Y., Ichimura, F., & Tsuji, A. (1988). Peritoneal transport of β‐lactam antibiotics: Effects of plasma protein binding and the interspecies relationship. Journal of Pharmaceutical Sciences, 77(7), 559-564. https://doi.org/10.1002/jps.2600770702