Effect of Histamine H2-receptor Antagonists on Acetaminophen and its Metabolites in Human Plasma
2004 年 30 巻 2 号 p. 67-71
詳細
2004 年 30 巻 2 号 p. 67-71
The effect of histamine H2-receptor antagonists on plasma concentrations of acetaminophen was investigated with respect to hepatic metabolism.
Acetaminophen (1000 mg) was administered orally together with ranitidine (300 mg), nizatidine (300 mg), nizatidine (150 mg) 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 120 min. and plasma acetaminophen glucuronide conjugate concentrations were significantly decreased from 15 to 45 min. 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 inhibi-tion of glucuronyltransferase. Therefore, care is necessary when administering acetaminophen together with ranitidine or nizatidine.
