Fig. 1

The experimental groups and treatment schedules. (1) Intrinsic XO and AO activities on vehicle. Crl:CD (low AO activity) and Jcl:SD rats (high AO activity) were orally administered vehicle once daily for 5 days. Urea samples were collected twice. One sample was collected before the administration of the vehicle to assess intrinsic AO activity. The other was collected after the administration of the vehicle and caffeine for the assessment of intrinsic XO activity. (2) Allopurinol pharmacokinetics on Febuxostat. Crl:CD rats (low AO activity) and Jcl:SD rats (high AO activity) were orally administered febuxostat (10 mg/kg) once daily for 5 days. Allopurinol (30 or 100 mg/kg) was administered orally. Blood samples were collected 0, 1, 2, 4, 8, 24, and 48 h after allopurinol administration. (3) Allopurinol pharmacokinetics on vehicle. Crl:CD (low AO activity) and Jcl:SD rats (high AO activity) were orally administered vehicle once daily for 5 days. Allopurinol (30 or 100 mg/kg) was orally administered. Blood samples were collected 0, 1, 2, 4, 8, 24, and 48 h after allopurinol administration. (4) Intrinsic XO and AO activities on febuxostat. Crl:CD (low AO activity) and Jcl:SD rats (high AO activity) were orally administered febuxostat once daily for 5 days. Urea samples were collected twice. One sample was collected before the administration of febuxostat to assess intrinsic AO activity. The other was collected after the administration of febuxostat and caffeine for the assessment of intrinsic XO activity