Nifedipine と Quinidine の薬物相互作用 The Mechanism of Pharmacokinetic Interaction between Nifedipine and Quinidine

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The purpose . of the present study was to evaluate the pharmacokinetic interaction between nifedipine and quinidine sulfate. To investigate any potential interaction, 6 male beagle dogs orally received 10 mg nifedipine or the combination of 10 mg nifedipine and 100 mg quinidine sulfate. These investigations were done using a randomized cross-over study design with a one-week wash-out period between treatments. Following the oral administration of nifedipine, the maximum serum concentration of nifedipine was signifi cantly increased by coadministration of quinidine sulfate. The mean residence time was significantly reduced by coadministration of quinidine sulfate. The dogs then received intravenously 4 mg nifedipine withor without 100 mg of oral quinidine sulfate . Following intravenous administration of nifedipine, the volume of distribution was significantly reduced, and the elimination rate constant was significantly increased by coadministra tion of quinidine sulfate.<BR>The effects of quinidine sulfate on the metabolism of nifedipine to metabolite (M-1) were studied using dog liver microsomes. Quinidine sulfate inhibited microsomal nifedipine oxidation in a noncompetitive manner. To determine whether quinidine sulfate interferes with the protein binding of nifedipine <I>in vitro</I>, the free fraction of nifedipine was determined by an ultracentrifugation technique. These data indicate that quinidine sulfate inhibits the binding of nifedipine to human albumin and α<SUB>1</SUB>-acid glycoprotein in a competitive manner. The results of the <I>in vitro</I> experiments suggest that quinidine sulfate inhibits the hepatic first pass metabolism and the serum protein binding of nifedipine. This pharmacokinetic interaction may result in an enhanced pharmacologic response.

収録刊行物

  • 臨床薬理 = JAPANESE JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS

    臨床薬理 = JAPANESE JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS 26(4), 793-801, 1995-12-31

    一般社団法人 日本臨床薬理学会

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各種コード

  • NII論文ID(NAID)
    10013831676
  • NII書誌ID(NCID)
    AN0025404X
  • 本文言語コード
    JPN
  • 資料種別
    ART
  • ISSN
    03881601
  • データ提供元
    CJP書誌  J-STAGE 
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