Febuxostat

The following compounds were purchased commercially from the sources indicated: allopurinol, benzbromarone, cyclosporine, D-fructose, elacridar, furosemide, hydrochlorothiazide, nicotinic acid, oxypurinol, rosuvastatin calcium salt, salicylic acid, 4-hydroxy chalcone (Wako Fine Chemical, Osaka, Japan); atorvastatin, chlorothiazide, febuxostat, mizoribine, pyrazinecarboxylic acid, ribavirin, tacrolimus, xylitol (Tokyo Chemical Industry, Tokyo, Japan); ethambutol, losartan (LKT Laboratories, St Paul, MN, USA); fenofibrate, probenecid, sulfasalazine, Ko143, ATP, AMP, creatine phosphate disodium salt tetrahydrate, creatine phosphokinase type I from rabbit muscle (Sigma-Aldrich, St. Louis, MO, USA); pyrazinamide (ACROS ORGANICS, Geel, Belgium); theophylline (Nacalai Tesque, Kyoto, Japan); and topiroxostat (MedChem Express, Princeton, NJ, USA). The [8-¹⁴C]-uric acid (53 mCi/mmol) was from American Radiolabeled Chemicals (St. Louis, MO, USA). All other chemicals used were commercially available and of analytical grade.

We administered deoxyribonuclease (DNase) I (Wako Pure Chemical Industries, Ltd., Osaka, Japan; 10 mg per kg body weight [BW] per day) intravenously via the tail vein^{35 (link)} or febuxostat (F0847, Tokyo Chemical Industry Co., Ltd., Tokyo, Japan; 5 mg per kg BW per day) intraperitoneally^{36 (link),37 (link)}. The control mice were injected with the same volume of the control vehicle (saline) 15 min prior to the experiment.
To deplete neutrophils, anti-granulocyte-differentiation antigen 1 (Gr-1; a major neutrophil marker) antibody (RB6-8C5, rat IgG2b) purified from the culture supernatants of a hybridoma (provided by Dr. R. Coffman) was intravenously administered into the mice (Gr-1 group) once every 3 days at a dose of 5 mg/kg BW^{37 (link),38 (link)} because the injection causes neutropenia for at least three days^{39 (link),40 (link)}. The control mice were also injected with an equivalent amount of normal rat IgG (Jackson Laboratories, Bar Harbor, ME) (IgG group).

Azilsartan, carvedilol, ciprofloxacin hydrochloride hydrate, dipyridamole, dantrolene sodium hydrate, furosemide, febuxostat, haloperidol, losartan potassium, lurasidone, montelukast sodium hydrate, and pioglitazone hydrochloride were purchased from Tokyo Chemical Industry Co., Ltd. Tamoxifen citrate and tosufloxacin tosylate hydrate were purchased from FUJIFILM Wako Pure Chemical Corporation. Raltegravir was extracted from the tablet. The manufacturers of the IR products are summarized in Table II.