BACKGROUND Some patients treated with ondansetron for postoperative nausea and vomiting do not respond to therapy. One possible mechanism for this failure is ultrarapid drug metabolism via the cytochrome P-450 system, specifically the enzyme 2D6 (CYP2D6). Ultrarapid metabolism is seen in patients with multiple functional copies (>/= 3) of the CYP2D6 allele. This study was designed to determine ...

BACKGROUND The impact of polymorphic cytochrome P450 CYP2D6 enzyme on oxycodone's metabolism and clinical efficacy is currently being discussed. However, there are only spare data from postoperative settings. The hypothesis of this study is that genotype dependent CYP2D6 activity influences plasma concentrations of oxycodone and its metabolites and impacts analgesic consumption. METHODS Patie...

There is growing consensus on the potential use of pharmacogenetics in clinical practice, and hopes have been expressed for application to the improvement of global health. However, two major challenges may lead to widening the "biotechnological gap" between the developing and the industrial world; first the unaffordability of some current technologies for poorer countries, and second the neces...

Studies were performed to determine the human enzymes responsible for the biotransformation of atomoxetine to its major metabolite, 4-hydroxyatomoxetine, and to a minor metabolite, N-desmethylatomoxetine. Utilizing human liver microsomes containing a full complement of cytochrome P450 (P450) enzymes, average K(m) and CL(int) values of 2.3 microM and 103 microl/min/mg, respectively, were obtaine...

The psychotropic beta-carboline alkaloids, showing high affinity for 5-hydroxytryptamine, dopamine, benzodiazepine, and imidazoline receptors and the stimulation of locus coeruleus neurons, are formed endogenously from tryptophan-derived indolealkylamines through the Pictet-Spengler condensation with aldehydes in both plants and mammals. Cytochromes P450 1A1 (18.5), 1A2 (20), and 2D6 (100) cata...

ously (7 ), and confirmed the proposed CYP2D6*35 haplotype (10 ). Phenotype-genotype correlation analysis subsequently showed that poor metabolizer status could effectively be ruled out by positive identification of a single functional 1584G-containing allelic variant in 43% of Caucasians but only 12% of African Americans. The 1584G assay can be performed directly on genomic DNA or on a long CY...

Polymorphisms in the cytochrome P450 2D6 (CYP2D6) gene are a major cause of pharmacokinetic variability in human. Although the poor metabolizer phenotype is known to be caused by two null alleles leading to absence of functional CYP2D6 protein, the large variability among individuals with functional alleles remains mostly unexplained. Thus, the goal of this study was to examine the intrinsic en...

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, ...

A series of antipeptide antibodies directed against CYP2D6 were produced by immunizing rabbits with peptides that were sterically unrestrained (linear) or conformationally restricted by cyclization. A variety of sites within the region comprising residues 254 to 290 of CYP2D6 were targeted. In immunoblotting studies, each of the antibodies against the linear and cyclic peptides recognized only ...

Tamoxifen has been used as adjuvant hormonal therapy for estrogen receptor positive breast cancer for over 30 years and is also widely used for the treatment of metastatic breast cancer. Tamoxifen is metabolized to its more active form by cytochrome P450 2D6 (CYP2D6); decreases in CYP2D6 activity, either by inactivating polymorphisms or drug interactions, can reduce concentrations of tamoxifen'...