Author/Authors :
Muramatsu، Shun نويسنده Division of Cancer Pathophysiology, National Cancer Center Research Institute, Tokyo, Japan , , Shiraishi، Seiji نويسنده Division of Cancer Pathophysiology, National Cancer Center Research Institute, Tokyo, Japan , , Miyano، Kanako نويسنده Division of Cancer Pathophysiology, National Cancer Center Research Institute, Tokyo, Japan , , Sudo، Yuka نويسنده Division of Cancer Pathophysiology, National Cancer Center Research Institute, Tokyo, Japan , , Toda، Akiko نويسنده Pharmacokinetics and Bioanalysis Center, Shin Nippon Biomedical Laboratories, Ltd., Wakayama, Japan , , Mogi، Masayuki نويسنده Pharmacokinetics and Bioanalysis Center, Shin Nippon Biomedical Laboratories, Ltd., Wakayama, Japan , , Hara، Mayumi نويسنده Division of Research and Development, Showa Yakuhin Kako Co., Ltd., Kawasaki, Japan , , Yokoyama، Akinobu نويسنده Division of Cancer Pathophysiology, National Cancer Center Research Institute, Tokyo, Japan , , Kawasaki، Yoshihiko نويسنده Division of Research and Development, Showa Yakuhin Kako Co., Ltd., Kawasaki, Japan , , Taniguchi، Mikio نويسنده Division of Research and Development, Showa Yakuhin Kako Co., Ltd., Kawasaki, Japan , , Uezono، Yasuhito نويسنده Division of Cancer Pathophysiology, National Cancer Center Research Institute, Tokyo, Japan ,
Abstract :
Acetaminophen, an analgesic and antipyretic drug, has been used clinically for more than a century. Previous studies showed that acetaminophen undergoes metabolic transformations to form an analgesic compound, N-(4-hydroxyphenyl) arachidonamide (AM404), in the rodent brain. However, these studies were performed with higher concentrations of acetaminophen than are used in humans. The aim of the present study was to examine the metabolism of AM404 from acetaminophen in the rat brain at a concentration of 20 mg/kg, which is used in therapeutic practice in humans, and to compare the pharmacokinetics between them. We used rat brains to investigate the metabolism of AM404 from acetaminophen at concentrations (20 mg/kg) used in humans. In addition, we determined the mean pharmacokinetic parameters for acetaminophen and its metabolites, including AM404. The maximum plasma concentrations of acetaminophen and AM404 in the rat brain were 15.8 µg/g and 150 pg/g, respectively, with corresponding AUC0-2h values of 8.96 μg hour/g and 117 pg hour/g. The tmax for both acetaminophen and AM404 was 0.25 hour. These data suggest that AM404’s concentration-time profile in the brain is similar to those of acetaminophen and its other metabolites. Measurement of blood acetaminophen concentration seems to reflect the concentration of the prospective bioactive substance, AM404.
