Search results for "CYP2B6"

Evaluation of Cytochrome P450 Activities in Human Hepatocytes In Vitro

2011

Major hepatic cytochrome P450 activities (CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4) can be simultaneously examined in human hepatocytes by incubation with a cocktail of multiple specific probes. Cocktail strategy in combination with mass spectrometry is shown to be a robust, fast, and sensitive procedure for P450 activity assessment. This procedure allows a drastic reduction of the number of cells required in the assay and sample analysis time and increases throughput and reproducibility. Major applications of the probe cocktail strategy are P450 phenotyping of hepatocytes and induction studies.

Cytochrome P450 reaction phenotyping and inhibition and induction studies of pinostrobin in human liver microsomes and hepatocytes

2017

Pinostrobin (PI, 5-hydroxy-7-methoxyflavanone) is a natural flavonoid known for its rich pharmacological activities. The objective of this study was to identify the human liver cytochrome P450 (CYP450) isoenzymes involved in the metabolism of PI. A single hydoxylated metabolite was obtained from PI after an incubation with pooled human liver microsomes (HLMs). The relative contributions of different CYP450s were evaluated using CYP450-selective inhibitors in HLMs and recombinant human CYP450 enzymes, and the results revealed the major involvement of CYP1A2, CYP2C9 and CYP2E1 in PI metabolism. We also evaluated the ability of PI to inhibit and induce human cytochrome P450 enzymes in vitro. H…

Re-expression of C/EBP alpha induces CYP2B6, CYP2C9 and CYP2D6 genes in HepG2 cells.

1998

Cytochrome P450 (CYP) activity is very low or even absent in human hepatomas, a phenomenon that is accompanied by low levels of some liver transcription factors, notably C/EBP alpha. To investigate a possible link between this transcription factor and hepatic CYP expression, we have stably transfected HepG2 cells with a C/EBP alpha vector containing a Zn-inducible metallothionein promoter. Expression of functional C/EBP alpha up to liver levels concomitantly increased the mRNAs of several members of the CYP2 family (2B6, 2C9 and 2D6), suggesting that this transcription factor may play a relevant role in controlling the hepatic expression of CYP enzymes.

[Pharmacogenomics of antiretrovirals].

2008

HIV infection is a serious but treatable disease, yet current treatment is limited by development of resistance and high rates of adverse drug reactions. Antiretroviral therapy is especially suitable for pharmacogenomic investigation as both drug exposure and treatment response can be reliably measured. Increasing knowledge about genes implicated in pharmacokinetics, mode of action, efficacy, and toxicity of drugs has already provided relevant results for clinical practice, for example: The strong association of the abacavir hypersensitivity reaction with HLA-B*5701 permits testing patients for the allele, and if present avoiding the drug and therefore preventing the reaction. Persons with …

Genotype and Allele Frequencies of Drug-Metabolizing Enzymes and Drug Transporter Genes Affecting Immunosuppressants in the Spanish White Population

2013

Interpatient variability in drug response can be widely explained by genetically determined differences in metabolizing enzymes, drug transporters, and drug targets, leading to different pharmacokinetic and/or pharmacodynamic behaviors of drugs. Genetic variations affect or do not affect drug responses depending on their influence on protein activity and the relevance of such proteins in the pathway of the drug. Also, the frequency of such genetic variations differs among populations, so the clinical relevance of a specific variation is not the same in all of them. In this study, a panel of 33 single nucleotide polymorphisms in 14 different genes (ABCB1, ABCC2, ABCG2, CYP2B6, CYP2C19, CYP2C…

Customised in vitro model to detect human metabolism-dependent idiosyncratic drug-induced liver injury

2017

Drug-induced liver injury (DILI) has a considerable impact on human health and is a major challenge in drug safety assessments. DILI is a frequent cause of liver injury and a leading reason for post-approval drug regulatory actions. Considerable variations in the expression levels of both cytochrome P450 (CYP) and conjugating enzymes have been described in humans, which could be responsible for increased susceptibility to DILI in some individuals. We herein explored the feasibility of the combined use of HepG2 cells co-transduced with multiple adenoviruses that encode drug-metabolising enzymes, and a high-content screening assay to evaluate metabolism-dependent drug toxicity and to identify…

Efavirenz and the CNS: what we already know and questions that need to be answered

2015

The NNRTI efavirenz has long been one of the most frequently employed antiretroviral drugs in the multidrug regimens used to treat HIV infection, in accordance with its well-demonstrated antiretroviral efficacy and favourable pharmacokinetics. However, growing concern about its adverse effects has sometimes led to efavirenz being replaced by other drugs in the initial treatment selection or to switching of therapy to efavirenz-free regimens in experienced patients. Neurological and neuropsychiatric reactions are the manifestations most frequently experienced by efavirenz-treated patients and range from transitory effects, such as nightmares, dizziness, insomnia, nervousness and lack of conc…

Cytochrome P450 enzymes as human autoantigens

1991

Cytochrome P-450 mRNA expression in human liver and its relationship with enzyme activity.

2001

CYP activity and protein contents have been measured in human liver using different techniques. In contrast, CYP mRNA data are scarce and the relationships between CYP mRNA contents and activities have not been established. These studies deserve further attention because mRNA determinations by RT-PCR require a very small amount of material (e.g., liver needle biopsy) and could provide important data regarding CYP expression regulation. In this study we measured in 12 human liver samples the mRNA contents of 10 CYPs by quantitative RT-PCR and the metabolic activities using specific substrates. mRNA contents and activities showed high correlation coefficients for CYP1A1, CYP1A2, CYP3A4, CYP2D…