The potent antioxidants licorice root extract and glabridin, an isoflavan purified from licorice root extract, were tested for their ability to modulate the activities of several cytochrome P450 (P450) enzymes. P450 3A4, the major human drug metabolizing P450 enzyme, was inactivated by licorice root extract and by glabridin in a time-and concentration-dependent manner. The inactivation was NADP...

Polymorphisms in the genes of drug-metabolizing enzymes have potential to contribute inter-individual differences drug pharmacokinetics and toxicity. A custom next-generation sequencing (NGS) panel was used 71 kidney transplanted patients study polymorphisms 11 relevant metabolism immunosuppressive drugs. Cyclosporine tacrolimus concentrations were determined by a validated liquid chromatograph...

Acetaminophen (APAP), a widely used analgesic and antipyretic agent, can cause acute hepatic necrosis in both humans and experimental animals when consumed in large doses. It is generally accepted that N-acetyl-p-benzoquinone imine (NAPQI) is the toxic, reactive intermediate whose formation from APAP is mediated by cytochrome P450. Several forms of P450 in humans, including 2E1, 1A2, 2A6, 3A4, ...

Background and Purpose The metabolic activity of cytochrome P450 (CYP) 2D6 is highly variable CYP2D6 genotypes insufficiently explain the extensive intermediate phenotypes, limiting prediction drug response plus adverse reactions. Since prototypic substrates are positively charged, aim this study was to evaluate organic cation transporters (OCTs) multidrug toxin extrusion proteins (MATEs) as po...

Correctly chosen D-optimal designs provide efficient experimental schemes when the aim of the investigation is to obtain precise estimates of parameters. In the current work, estimates of parameters refer to the enzyme kinetic parameters Vmax and Km, but they also refer to the inhibition constant Ki. In general, this experimental approach is performed on a grid of values of the design variables...

dacarbazine (dtic) is a synthetic chemical antitumor agent which is used to treat malignant melanoma and hodgkin’s disease. dtic is a prodrug which is converted to an active form undergoing demethylation by liver enzymes. the active form prevents the progress of disease via alkylation of dna strand. in the structure of this drug, the imidazole ring, a triazen chain and carboxamide group exist. ...

The synthetic opioid fentanyl undergoes extensive metabolism in humans. Systemic elimination occurs primarily by hepatic metabolism. When administered as a lozenge for oral transmucosal absorption, swallowed fentanyl is subject to first pass metabolism in the liver and possibly small intestine. Little is known, however, about the identity and formation of human fentanyl metabolites. This invest...

Correctly chosen D-optimal designs provide efficient experimental schemes when the aim of the investigation is to obtain precise estimates of parameters. In the current work, estimates of parameters refer to the enzyme kinetic parameters Vmax and Km, but they also refer to the inhibition constant Ki. In general, this experimental approach is performed on a grid of values of the design variables...