Carbazeran

The human vasculature S9 fractions obtained as a gift from BioIVT (Baltimore, MD) were prepared from the interior linings of iliac arteries collected during standard liver harvesting. The yield of vascular S9 per weight of tissue was calculated from the total protein yielded from the preparation as measured by the BCA protein assay (Thermo Fisher Scientific, Rockford, IL) divided by the weight of tissue used in the preparation, and this is represented as the average of three donors (one male and two females). The human kidney (whole kidney, mixed sex, pool of 8), lung (nonsmoker, mixed sex, pool of 4), and intestinal (duodenal and jejunal, prepared by elution, mixed sex, pool of 15) S9 fractions were procured from XenoTech (Kansas City, KS). Human liver S9 fractions were procured from BioIVT (mixed sex, pool of 150). Carbazeran and 4-oxoCarbazeran were procured from Toronto Research Chemicals (Ontario, Canada), and hydralazine was procured from Sigma Aldrich (St. Louis, MO). Dialysis membranes (6-8 kDa molecular mass cut-off) for protein binding were procured from HTDialysis (Gales Ferry, CT). Water and acetonitrile were of HPLC grade and were procured from Fisher Scientific (Fair Lawn, NJ). All other reagents used in the study were of extrapure grade.

Dextrorphan tartrate, diclofenac sodium salt, 4-hydroxydiclofenac, S-mephenytoin, 4-hydroxyquinoline, paclitaxel, and testosterone were purchased from Cayman Chemical (Ann Arbor, MI). 7-Hydroxycoumarin was purchased from Chem Service (West Chester, PA). Benzydamine N-oxide, 7-Hydroxycoumarin sulfate potassium salt, kynuramine hydrobromide, and N-acetyl sulfamethazine were obtained from Santa Cruz Biotechnology (Dallas, TX). 4-Acetamidobenzoic acid, p-acetamidophenyl b-D-glucuronide sodium salt, 4-aminobenzoic acid, benzydamine hydrochloride, chlorzoxazone, coumarin, dextromethorphan hydrobromide, 6b-hydroxytestosterone, 7-Hydroxycoumarin b-D-glucuronide sodium salt, 7-ethoxycoumarin, paracetamol sulfate potassium, phenacetin, and sulfamethazine were purchased from Sigma-Aldrich (St. Louis, MO). Carbazeran, 4-hydroxyCarbazeran, 6-hydroxychlorzoxazone, 6a-hydroxypaclitaxel, acetaminophen glutathione disodium salt, midazolam, 19-hydroxymidazolam, and 4-hydroxy-S-mephenytoin were obtained from Toronto Research Chemicals (Toronto, ON, Canada). All other drug-metabolizing enzyme substrates were obtained from Sigma-Aldrich.