Effects of spice constituents on P-glycoprotein-mediated transport and CYP3A4-mediated metabolism in vitro.

Effects of Spice Constituents on P-gp-mediated Transport and Cyp3a4-mediated Metabolism in Vitro

Influence of P-glycoprotein on the transport and metabolism of indinavir in Caco-2 cells expressing cytochrome P-450 3A4.

Caco-2 cells grown in the presence of 1alpha,25-di-OH vitamin D(3) (di-OH vit D(3)) were used as a model to evaluate the effects of P-glycoprotein (Pgp) efflux on CYP3A4-mediated metabolism of indinavir during intestinal absorption. Caco-2 cells grown under these conditions demonstrated significant CYP3A4 activity and maintained Pgp-mediated directional transport of indinavir. Metabolism of ind...

Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4.

Dietary constituents (e.g., in grapefruit juice; NaCl) and phytochemicals (e.g., St. John's wort) are important agents modifying drug metabolism and transport and thereby contribute to interindividual variability in drug disposition. Most of these drug-food interactions are due to induction or inhibition of P-glycoprotein and/or CYP3A4. Preliminary data indicate that piperine, a major component...

Identification of the active components in Shenmai injection that differentially affect Cyp3a4-mediated 1'-hydroxylation and 4-hydroxylation of midazolam.

Shenmai injection (SMI) is a popular herbal preparation that is widely used for the treatment of atherosclerotic coronary heart disease and viral myocarditis. In our previous study, SMI was shown to differentially affect CYP3A4-mediated 1'-hydroxylation and 4-hydroxylation of midazolam (MDZ). The present study was conducted to identify the active components in SMI responsible for the differenti...

The effects of fruit juices on drug disposition: a new model for drug interactions.

Grapefruit juice produces mechanism-based inhibition of intestinal drug metabolism when consumed in normal quantities. This can produce clinically important increases in oral drug bioavailability when coadministered with substrates of cytochrome p450 3A4 (CYP3A4) that undergo high presystemic metabolism. Furanocoumarins such as bergamottin and 6',7'-dihydroxybergamottin have been identified as ...