Nitrofurantoin and other agents are actively transported into human and rodent milk. The purpose of this study was to determine whether nitrofurantoin active transport across mammary epithelia occurs basolaterally or apically, using the CIT3 cell culture model of lactation. The CIT3 model actively transports nitrofurantoin in the basolateral to apical direction. Basolateral to apical permeabili...

Tanaproget is a first-in-class nonsteroidal progesterone receptor agonist that is being investigated for use in contraception. A major in vitro and in vivo metabolite of tanaproget formed in humans was initially characterized as a glucuronide of tanaproget. However, whether the glucuronide was linked to the nitrogen or sulfur of the benzoxazine-2-thione group in tanaproget could not be determin...

N*-nitrosonornicotine (NNN) induces tumors in the rat nasal cavity and esophagus and is believed to be a causative agent for esophageal cancer in tobacco users. To exert its carcinogenic potential, NNN must be metabolically activated by a-hydroxylation at either the 2*or 5*-carbon. We previously reported that the human cytochrome P450 (P450), 2A6, efficiently and specifically catalyzed NNN 5*-h...

UDP-glucuronosyltransferases (UGTs) are major phase II drug metabolism enzymes that catalyze the glucuronidation of numerous endogenous and exogenous compounds. UGTs are divided into two families, UGT1 and UGT2, based on evolutionary divergence and homology. Nine UGT1A and seven UGT2B functional isoforms have been identified in humans. Glucuronidation occurs mainly in liver but also in various ...

UDP-glucuronosyltransferases (UGTs) are major phase II drug metabolism enzymes that catalyze the glucuronidation of numerous endogenous and exogenous compounds. UGTs are divided into two families, UGT1 and UGT2, based on evolutionary divergence and homology. Nine UGT1A and seven UGT2B functional isoforms have been identified in humans. Glucuronidation occurs mainly in liver but also in various ...

The effect of common organic solvents on the activities of various human cytochromes P450 has been reported. However, very little is known about their influence on CYP2B6 and CYP2C8 enzymes. The purpose of this study was to investigate the effect of solvents on the kinetics of representative CYP2B6 (bupropion hydroxylase) and CYP2C8 (paclitaxel hydroxylase) reactions in human liver microsomes. ...

Imatinib, a potent and selective protein tyrosine kinase inhibitor, has been approved for the treatment of chronic myelogenous leukemia and metastatic and unresectable malignant gastrointestinal stromal tumors. In vitro metabolism of imatinib was investigated in rat and human liver microsomes. Besides several oxidative metabolites and an N-desmethyl metabolite, as previous reported, a novel met...

Ellagic acid (EA), a polyphenol present in berries, has been demonstrated to be preventive of esophageal and colon cancer in animals. Here, we have studied the ability of organic anion transporters (OATs) and organic anion-transporting polypeptides (OATPs) to transport EA. The accumulation of radiolabeled [C]EA, [H]p-aminohippuric acid (PAH), [C]glutarate, [H]estrone sulfate, [H]ochratoxin A, a...

The possibility of interactions between natural products/supplements and conventional prescription medicines is one of the most important issues in pharmacotherapeutic safety. Recently, we reported that some terpenoids such as (R)-( )-citronellal and glycyrrhetic acid, which are present in herbal medicines, can act as inhibitors of P-glycoprotein (MDR1/ABCB1). In the present study, the effects ...

MK-0767 (KRP-297; 2-methoxy-5-(2,4-dioxo-5-thiazolidinyl)-N-[[4(trifluoromethyl)phenyl] methyl]benzamide) is a thiazolidinedione (TZD)-containing dual agonist of the peroxisome proliferator-activated receptors and that has been studied as a potential treatment for patients with type 2 diabetes. The metabolism and excretion of [C]MK-0767 were evaluated in six human volunteers after a 5-mg (200 C...