Effect of Histamine H_2-receptor Antagonists on Acetaminophen and its Metabolites in Human Plasma
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概要
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The effect of histamine H_2-receptor antagonists on plasma concentrations of acetaminophen was investigated with respect to hepatic metabolism. Acetaminophen (1000mg) was administered orally together with ranitidine (300mg), nizatidine (300mg), nizatidine (150mg) or placebo to five healthy male volunteers. Venous blood samples were taken before and after administration and plasma acetaminophen and acetaminophen conjugates (glucuronide and sulphate) were measured by high-performance liquid chromatography. The pharmacokinetic parameters were calculated from the plasma acetaminophen concentration-time curves for each volunteer. With ranitidine, compared with placebo, plasma acetaminophen concentrations were significantly increased from 15 to 120min. and plasma acetaminophen glucuronide conjugate concentrations were significantly decreased from 15 to 45min. With nizatidine, as compared with placebo, plasma acetaminophen concentrations were significantly increased from 45 to 120 min. and 45 to 60 min. for the high and low doses of the drug, respectively. Acetaminophen glucuronide concentrations were significantly decreased from 30 to 45 min. and at 30 min., respectively, for the high and low doses of nizatidine, respectively. However, with ranitidine and nizatidine, plasma acetaminophen sulphate concentrations were not significantly altered. Co-administration with ranitidine or nizatidine reduces plasma acetaminophen glucuronide concentrations and increases plasma acetaminophen concentrations dose-dependently. These effects of ranitidine and nizatidine could result from inhibition of glucuronyltransferase. Therefore, care is necessary when administering acetaminophen together with ranitidine or nizatidine.
- 日本医療薬学会の論文
- 2004-02-10
著者
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ITOH Hiroki
Department of Physics, Faculty of Science, Hokkaido University
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TAKEYAMA MASAHARU
Department of Anesthesiology and Critical Care Medicine, Kagoshima University School of Medicine
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Itoh Hiroki
Department Of Cardiology Tokyo Women's Medical University
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Takeyama Masaharu
Department Of Anesthesiology And Critical Care Medicine Kagoshima University School Of Medicine
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Takeyama Masaharu
Department Of Clinical Pharmacy Oita University Hospital
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Itoh Hiroki
Department Of Clinical Pharmacy Oita University Hospital
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