Search results for "CYP"
showing 10 items of 480 documents
Severe Tremor After Cotrimoxazole-Induced Elevation of Venlafaxine Serum Concentrations in a Patient With Major Depressive Disorder
2013
: We describe a female patient who was an extensive metabolizer of cytochrome P450 isoenzyme (CYP) 2D6 and an intermediate metabolizer of CYP2C19 (genotype: CYP2C19 *1/*2). She exhibited high serum concentrations of venlafaxine and O-desmethylvenlafaxine and developed severe tremor after comedication with cotrimoxazole (sulfamethazole/trimethoprim). Venlafaxine is mainly metabolized by O- and N-demethylation. O-demethylation is catalyzed by the highly polymorphic CYP2D6 and N-demethylation by several enzymes, CYP2C19, CYP2C9, and CYP3A4. The observed overall pharmacokinetic effect was most probably the result of decreased N-demethylation of venlafaxine by (1) reduced expression of CYP2C19 d…
Effects of steatosis on drug-metabolizing capability of primary human hepatocytes.
2007
Abstract The suitability of liver grafts discarded for transplantation because of macrosteatosis for preparing human hepatocyte cultures for in vitro drug metabolism studies has been examined. Lower cell viability and yield of isolation procedure were obtained from fatty livers (>40% steatosis) with respect to normal tissue. Significant reductions in 7-ethoxycoumarin O-deethylation (ECOD) and testosterone oxidations were found in hepatocytes prepared from steatotic livers. The potential impact of lipid accumulation on P450 enzymes was studied in vitro by incubation of cultured hepatocytes with long chain free fatty acids (FFA). Treatment of cells with 0.25–3 mM FFA induced dose-dependent ac…
Anti-androgens for the treatment of hirsutism.
2002
Many alternatives exist for treating hirsutism. Based on an analysis of scientific literature and on the experiences of the author, the most common anti-androgen agents are discussed in this review. Androgen receptor blockers (cyproterone acetate, flutamide and spironolactone), 5 alpha-reductase inhibitors (finasteride) and androgen-suppressing agents (gonadotrophin-releasing hormone [GnRH] agonists, oestroprogestins, corticosteroids and insulin-sensitising agents) are evaluated and compared. The importance of diagnosis in choosing the most appropriate anti-androgen treatment is also discussed.
18-hydroxylation in the Y-1 adrenal cell line: response to ACTH and to culture conditions.
1992
The 18-hydroxylation of deoxycorticosterone in the Y-1 adrenal cell line was studied under various incubation and cell culture conditions and compared to 11 beta-hydroxylation. Repeated incubation of the substrate increased both 18- and 11 beta-hydroxylation in the Y-1 cells. Furthermore, both 18- and 11 beta-hydroxylation were increased with increased serum concentration and prolonged incubation time. While the increase in 11 beta-hydroxylation seemed to be independent of the type of serum, 18-hydroxylation was much more important in cells cultured in fetal or newborn calf serum supplemented medium than in those cultured in horse serum supplemented medium. As expected, ACTH treatment incre…
3H-cyproterone acetate: binding characteristics to human uterine progestagen receptors
1985
The availability of tritium labeled cyproterone acetate (CPA) facilitated the systematic investigation of the binding characteristics of this compound for human uterine progesterone receptors (PgR). The binding parameters of 3H-CPA are compared to those of 3H-R5020 and 3H-progesterone. The rate constants of association (k1M-1sec-1) to PgR were 7.8 X 10(3) for 3H-R5020, 4.5 X 10(4) for 3H-progesterone and 4.0 X 10(4) for 3H-CPA. The rate constants of dissociation (k-1, sec-1) were 3.6 X 10(-5) for 3H-R5020, 21.3 X 10(-5) for 3H-progesterone and 17.8 X 10(-5) for 3H-CPA. The Kd-values (M), as obtained by titration analysis and subsequent Scatchard plot analysis were 1.2 X 10(-9) for 3H-R5020,…
Genotype-driven pharmacokinetic simulations of warfarin levels in Puerto Ricans.
2020
Abstract Objectives The inter-individual variability of warfarin dosing has been linked to genetic polymorphisms. This study was aimed at performing genotype-driven pharmacokinetic (PK) simulations to predict warfarin levels in Puerto Ricans. Methods Analysis of each individual dataset was performed by one-compartmental modeling using WinNonlin®v6.4. The k e of warfarin given a cytochrome P450 2C9 (CYP2C9) genotype ranged from 0.0189 to 0.0075 h−1. K a and V d parameters were taken from literature. Data from 128 subjects were divided into two groups (i.e., wild-types and carriers) and statistical analyses of PK parameters were performed by unpaired t-tests. Results In the carrier group (n=6…
The Val432Leu polymorphism of the CYP1B1 gene is associated with differences in estrogen metabolism and bone density.
2009
Polymorphisms of the CYP450 genes that encode for the enzymes that metabolize estrogen are linked to hormone-related cancers. We investigated the impact of two polymorphisms of the CYP1B1 gene previously reported to be associated with hormone-related disorders on estrogen metabolism and bone mineral density (BMD), another hormone-dependent condition, in women from different ethnic backgrounds. Four hundred sixty-eight postmenopausal Caucasian women, 220 from St. Louis, MO, USA (mean age=63.5+/-0.53 years) and 248 from Palermo, Italy (mean age=72.9+/-0.44 years) participated in the study. Measurements of urinary estrogen metabolites by enzyme-linked immunoassay, serum estradiol by ultrasensi…
Tissue bioaccumulation patterns, xenobiotic biotransformation and steroid hormone levels in Atlantic salmon (Salmo salar) fed a diet containing perfl…
2011
In the present study, groups of juvenile Atlantic salmon (Salmo salar) were fed gelatine capsules containing fish-food spiked with PFOA or PFOS (0.2 mg kg(-1) fish) and solvent (methanol). The capsules were given at days 0, 3 and 6. Blood, liver and whole kidney samples were collected prior to exposure (no solvent control), and at days 2, 5, 8 and 14 after exposure (Note: that day 14 after exposure is equal to 7d recovery period). We report on the differences in the tissue bioaccumulation patterns of PFOS and PFOA, in addition to tissue and compound differences in modulation pattern of biotransformation enzyme genes. We observed that the level of PFOS and PFOA increased in the blood, liver …
Effect of CYP1A1 Gene Polymorphisms on Estrogen Metabolism and Bone Density
2004
UNLABELLED: In this study, we evaluated the effect of polymorphisms of the CYP1A1 gene, linked to hormone-related cancers, on estrogen metabolism and BMD. We found that variants carrying the A allele (CA and AA) for the C4887A polymorphism have a significantly higher degree of estrogen catabolism and lower femoral BMD. INTRODUCTION: Polymorphisms of the CYP1A1 gene, one of the key enzymes that metabolize estrogen, have been linked with hormone-related cancers. We investigated the impact of these polymorphisms on estrogen metabolism and BMD, which is another hormone-dependent health issue. MATERIALS AND METHODS: One hundred seventy postmenopausal women (mean age, 63.5 +/- 0.6 years) particip…
Comparative effects of UVA and UVB irradiation on the immune system of fish.
2000
Aquatic organisms can be harmed by the current levels of solar ultraviolet radiation. We have recently shown that exposure of fish to UVB irradiation alters the functioning of the fish immune system, but the effects of UVA radiation are unknown. The present study continues this work by characterizing UVA irradiation-induced immunological changes in fish. Roach, a cyprinid fish, were exposed to a single dose of either UVA (3.6 J/cm2) or UVB (0.5 J/cm2) irradiation. Both irradiations suppressed transiently mitogen-stimulated proliferation of blood lymphocytes. UVA, but not UVB, decreased hematocrit, plasma protein, and plasma immunoglobulin levels and increased the proportions of blood cells …