Association between nonalcoholic hepatic steatosis and hepatic cytochrome P-450 3A activity.

Background & Aims: Comorbidities associated with nonalcoholic fatty liver often require therapy with medications (eg, statins) metabolized by cytochrome P-450 3A (CYP3A). There is significant interindividual variability in CYP3A expression. However, human studies that systematically examined the relationship between hepatic steatosis and hepatic CYP3A activity are lacking.

Spherical agglomeration of mefenamic acid and nabumetone to improve micromeritics and solubility: a technical note.

Spherical agglomeration techniques were developed for improving the flow and compressibility characteristics of microcrystalline mefenamic acid and nabumetone. The process involved agglomerating microcrystals using agglomerating solvents. Temperature and speed of agitation were optimized to obtain spherical agglomerates in a desired range, which was found to be essential to enhance compressibility.

Vincristine transcriptional regulation of efflux drug transporters in carcinoma cell lines.

The increased expression of drug transporters following cancer chemotherapy contributes to resistance. This may reflect transcriptional up-regulation and/or clonal selection. We quantified the expression of mRNA for ABCB1 (mdr1), ABCC1 (mrp1), ABCC2 (mrp2) and ABCC3 (mrp3) to evaluate the potential contribution of induction.

Activity of CYP2E1 and CYP3A enzymes in adults with moderate alcohol consumption: a comparison with nonalcoholics.

Alcohol consumption is known to induce hepatic CYP2E1 activity, but its effect on hepatic and intestinal CYP3A in humans is not known. We have conducted a study to compare the CYP2E1 and CYP3A activities in 20 individuals with moderate alcohol consumption and 20 gender-, race-. and body mass index (BMI)-matched nonalcoholics.

Inhibition of human intestinal wall metabolism by macrolide antibiotics: effect of clarithromycin on cytochrome P450 3A4/5 activity and expression.

Background: Clarithromycin increases both hepatic and intestinal availability of the selective cytochrome P450 (CYP) 3A probe midazolam. This study was designed to identify determinants of variability in the extent of intestinal wall CYP3A inhibition by clarithromycin, such as CYP3A5 genotype, and the mechanism of inhibition.

Methods: Ten healthy volunteers received 500 mg oral clarithromycin twice a day for 7 days.

Is adiponectin involved in the pathogenesis of nonalcoholic steatohepatitis? A preliminary human study.

Background: Animal studies have suggested that adiponectin may play a role in the pathogenesis of alcoholic and nonalcoholic fatty liver disease. Studies are limited that evaluated the role of adiponectin in the pathogenesis of nonalcoholic steatohepatitis (NASH).

Methods: To further our understanding of the role of adiponectin in the pathogenesis of NASH, the following studies were conducted.

Expression and function of ABCB1 and ABCG2 in human placental tissue.

The placenta plays an important role in modulating xenobiotic passage from mother to fetus. Studies in mice have demonstrated that placental ABCB1 and ABCG2 can affect the transfer of drugs across the placental barrier, suggesting a role for these transporters in protecting the fetus from environmental toxicants or drugs ingested by the mother during pregnancy. To assess the role of these transporters in the human placenta, studies were conducted to evaluate the expression and functional activity of placental ABCB1 and ABCG2.

Activation of CYP2C9-mediated metabolism by a series of dapsone analogs: kinetics and structural requirements.

Cytochrome P450 2C9-mediated metabolism has been shown to be activated in the presence of the effector dapsone. However, it has yet to be established what effector structural features are necessary to activate CYP2C9 activity. To address this question, kinetic studies were conducted with nine analogs of dapsone containing various functional properties (three sulfone compounds, three carbonyl compounds, and three sulfonamide compounds), to examine the functional groups important for enzyme activation by the effector (dapsone).