Effects of peritoneal dialysis on pharmacotherapy: A deductive pharmacokinetic-model approach to predict drug concentration profiles in plasma and peritoneal fluid

Mizuki Horiuchi, Soichiro Moriyama, Yukiko Takahata, Tetsuya Aiba, Yuji Kurosaki

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

The aim of this study was to present a deductive compartment pharmacokinetic (PK) model to predict the concentration profiles of drugs in plasma and peritoneal fluid in peritoneal dialysis (PD) rats. PK parameters of model drugs in normal and experimentally induced acute renal failure (ARF) rats not undergoing PD were obtained inductively in a common regression manner with a two-compartment model. In PD normal and ARF rats, PK parameters relating to the transfer of drugs to the peritoneal dialysate and the progress of renal failure were deductively modified to simulate the drug concentration-time profiles in plasma and in the peritoneal fluid in PD rats. The deductively introduced modifiers were the volume of distribution in the peripheral compartment, plasma protein binding, and solvent movement factor to the peritoneal fluid. Predicted profiles of tolbutamide, propranolol and cefazolin in PD normal and ARF rats were compared with the corresponding observed data. This minimal deductive approach yielded satisfactory accuracy in the prediction of both the plasma and peritoneal fluid concentrations of tolbutamide and propranolol.

Original languageEnglish
Pages (from-to)154-161
Number of pages8
JournalDrug Metabolism And Pharmacokinetics
Volume29
Issue number2
DOIs
Publication statusPublished - 2014

Keywords

  • Acute renal failure
  • Cefazolin
  • Deductive PK model
  • Peritoneal dialysis
  • Pharmacokinetics
  • Profile prediction
  • Propranolol
  • Rat
  • Tolbutamide

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

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