ヒト及びラットの肝細胞培養系を用いた薬物暴露によるMDR1, MRP1, MRP2及びMRP3 mRNA発現変動 Peritoneal Dialysis Alters Tolbutamide Pharmacokinetics in Rats with Experimental Acute Renal Failure

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著者

    • AIBA Tetsuya
    • Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
    • HORIUCHI Mizuki
    • Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
    • MAKITA Takashi
    • Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
    • KOMORI Yukiko
    • Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
    • KAWASAKI Hiromu
    • Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
    • KUROSAKI Yuji
    • Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University

抄録

  The plasma concentration profile of the antidiabetic agent tolbutamide was investigated in glycerol-induced acute renal failure (ARF) rats receiving or not receiving peritoneal dialysis (PD) to assess the impact of performing dialysis on tolbutamide pharmacokinetics. It was revealed that the plasma concentration of tolbutamide was decreased by 23.4% by performing PD in ARF rats, while it was not changed by PD in normal rats. The decrease in the plasma concentration of tolbutamide was nearly proportional to the increase in its volume of distribution. To clarify the mechanisms responsible for the decreased tolbutamide concentration caused by PD, the plasma protein binding of tolbutamide was examined in normal and ARF rats. The plasma unbound fraction of tolbutamide was higher in ARF rats than in normal rats, and the dissociation constants were 3.5±0.7 and 5.5±0.2 μg/mL in normal and ARF rats, respectively. These results indicated that the unbound fraction of tolbutamide was increased in ARF rats because of its protein binding being suppressed. It is therefore likely that since a measurable amount of tolbutamide can distribute in peritoneal dialysate in ARF rats, but not in normal rats, the plasma concentration of tolbutamide was decreased by performing PD only in ARF rats. These findings suggest that diabetes medication with tolbutamide should be carefully performed in patients receiving dialysis treatment.<br>

収録刊行物

  • Drug metabolism and pharmacokinetics  

    Drug metabolism and pharmacokinetics 21(4), 291-296, 2006-08-31 

    The Japanese Society for the Study of Xenobiotics

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各種コード

  • NII論文ID(NAID)
    10018042852
  • NII書誌ID(NCID)
    AA1162652X
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    13474367
  • データ提供元
    CJP書誌  CJP引用  J-STAGE 
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