Biol. Pharm. Bull. 30(1) 157—161 (2007)

wide, but in Japan, APAP is used mainly as an antipyretic in children. APAP is rarely used as an analgesic in Japan, because the recommended dosage of APAP in Japan (less than 1500 mg/d) is lower than that in United States (less than 4000 mg/d). APAP is metabolized by UDP-glucuronosyltransferase, sulfotransferase and cytochrome P450 (Fig. 1). There is substantial interindividual variability in APAP glucuronidation, and polymorphisms of UDP-glucuronosyltransferase have been reported. APAP is metabolized by cytochrome P450 2E1 to the toxic metabolite N-acetyl-p-benzoquinone-imine (NAPQI). The genotype frequency of cytochrome P450 2E1 differs with ethnicity. The degree of chlorzoxazone clearance, which is used as a phenotypic probe of CYP2E1 enzyme activity in Japanese, is lower in Caucasians. Therefore, the pharmacokinetics of APAP in high doses in Japanese patients needs to be clarified to determine whether the use of APAP as an analgesic is safe. The relationship between pain relief and APAP concentration has been investigated in German and Danish postoperative patients. In children undergoing adenotonsillectomy, the pharmacokinetic-pharmacodynamic model has been described. However, pain sensitivity differs among ethnic groups. A better understanding of the dose–effect relationship in Japanese is needed to control chronic pain. There are no data describing the pharmacokinetics and pharmacodynamics of APAP and its metabolites in the Japanese. An understanding of the relationship between the analgesic effect and the time after APAP administration is important for determining the dosage of APAP for the treatment of chronic pain. The aims of this study are to characterize the pharmacokinetics and pharmacodynamics of APAP and to determine an effective APAP regimen in Japanese patients with chronic pain.