Efficacy of peritoneal dialysis of tolbutamide in rats under conditions of the plasma unbound fraction being increased

Takashi Makita, Tetsuya Aiba, Yuki Izuwa, Yukiko Komori, Hiromu Kawasaki, Yuji Kurosaki

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Peritoneal dialysis of a highly protein-bound compound, tolbutamide, was examined in rats to clarify whether the efficacy of the peritoneal dialysis of such compounds increases proportionally as their unbound fractions increase. As expected, it was shown that the tolbutamide concentration of the peritoneal dialysate rose as the unbound fraction of tolbutamide increased. However, the efficacy of peritoneal dialysis of tolbutamide was proportionally elevated only when the unbound fraction was slightly increased by sulfamethoxazole treatment. When the unbound fraction of tolbutamide was increased 7.8 times by sulfadimethoxine treatment, the dialysis efficacy was increased to only 58% of that expected. This discrepancy between the observed and expected values regarding dialysis efficacy was more marked when experiments were performed in rats with experimentally induced acute renal failure. Pharmacokinetic analysis indicated that the intrinsic dialysis clearance of tolbutamide decreased when its unbound fraction was greatly increased. These findings suggest that peritoneal dialysis may be mediated not only by passive diffusion, but also by concentration-dependent processes. The efficacy of the peritoneal dialysis of therapeutic compounds may be overestimated if the estimation is based only on their unbound fraction measured under control conditions.

Original languageEnglish
Pages (from-to)1-8
Number of pages8
JournalBiopharmaceutics and Drug Disposition
Volume30
Issue number1
DOIs
Publication statusPublished - Feb 17 2009

Keywords

  • Acute renal failure
  • Peritoneal dialysis
  • Protein binding
  • Sulfonamides
  • Tolbutamide

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

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