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1.
Characterization of the human cytochrome P450 enzymes involved in the metabolism of dihydrocodeine 总被引:1,自引:0,他引:1
L. C. Kirkwood R. L. Nation & A. A. Somogyi 《British journal of clinical pharmacology》1997,44(6):549-555
Aims Using human liver microsomes from donors of the CYP2D6 poor and extensive metabolizer genotypes, the role of individual cytochromes P-450 in the oxidative metabolism of dihydrocodeine was investigated.
Methods The kinetics of formation of N- and O -demethylated metabolites, nordihydrocodeine and dihydromorphine, were determined using microsomes from six extensive and one poor metabolizer and the effects of chemical inhibitors selective for individual P-450 enzymes of the 1A, 2A, 2C, 2D, 2E and 3A families and of LKM1 (anti-CYP2D6) antibodies were studied.
Results Nordihydrocodeine was the major metabolite in both poor and extensive metabolizers. Kinetic constants for N -demethylation derived from the single enzyme Michaelis-Menten model did not differ between the two groups. Troleandomycin and erythromycin selectively inhibited N -demethylation in both extensive and poor metabolizers. The CYP3A inducer, α-naphthoflavone, increased N -demethylation rates. The kinetics of formation of dihydromorphine in both groups were best described by a single enzyme Michaelis-Menten model although inhibition studies in extensive metabolizers suggested involvement of two enzymes with similar K m values. The kinetic constants for O -demethylation were significantly different in extensive and poor metabolizers. The extensive metabolizers had a mean intrinsic clearance to dihydromorphine more than ten times greater than the poor metabolizer. The CYP2D6 chemical inhibitors, quinidine and quinine, and LKM1 antibodies inhibited O -demethylation in extensive metabolizers; no effect was observed in microsomes from a poor metabolizer.
Conclusions CYP2D6 is the major enzyme mediating O -demethylation of dihydrocodeine to dihydromorphine. In contrast, nordihydrocodeine formation is predominantly catalysed by CYP3A. 相似文献
Methods The kinetics of formation of N- and O -demethylated metabolites, nordihydrocodeine and dihydromorphine, were determined using microsomes from six extensive and one poor metabolizer and the effects of chemical inhibitors selective for individual P-450 enzymes of the 1A, 2A, 2C, 2D, 2E and 3A families and of LKM1 (anti-CYP2D6) antibodies were studied.
Results Nordihydrocodeine was the major metabolite in both poor and extensive metabolizers. Kinetic constants for N -demethylation derived from the single enzyme Michaelis-Menten model did not differ between the two groups. Troleandomycin and erythromycin selectively inhibited N -demethylation in both extensive and poor metabolizers. The CYP3A inducer, α-naphthoflavone, increased N -demethylation rates. The kinetics of formation of dihydromorphine in both groups were best described by a single enzyme Michaelis-Menten model although inhibition studies in extensive metabolizers suggested involvement of two enzymes with similar K
Conclusions CYP2D6 is the major enzyme mediating O -demethylation of dihydrocodeine to dihydromorphine. In contrast, nordihydrocodeine formation is predominantly catalysed by CYP3A. 相似文献
2.
Linking the Disabilities of Arm, Shoulder, and Hand to the International Classification of Functioning, Disability, and Health. 总被引:1,自引:0,他引:1
Adriana Silva Drummond Rosana Ferreira Sampaio Marisa Cotta Mancini Renata Noce Kirkwood Tanja A Stamm 《Journal of hand therapy》2007,20(4):336-43; quiz 344
The objective of this study was to explore whether the items from a specific outcome measure, that is, Disabilities of the Arm, Shoulder, and Hand (DASH), for quantifying limb symptoms and functions in musculoskeletal disorders fit into the framework of the International Classification of Functioning, Disability and Health (ICF). All DASH items were compared to the ICF according to eight linking rules. Two groups of researchers performed the linking independently, and the results were compared by correlation. The 30 DASH items and four items from the optional modules were linked to 63 ICF categories and 11 chapters: 15 categories belong to the ICF body functions component and 48 to the activities and participation component. There were no items coded under the components body structure or environmental factors. Kappa index showed an agreement of 0.73 (p<0.001). The results showed that the content of the DASH does link well with the ICF framework. Clinicians and researchers must attend to the fact that certain domains and categories from the ICF are not covered by the DASH. Limitations of the instrument may be overcome by simultaneously using other instruments that address the intended content. 相似文献
3.
Factors influencing women to undergo screening mammography 总被引:2,自引:0,他引:2
4.
Braffman BH; Coleman BG; Ramchandani P; Arger PH; Nodine CF; Dinsmore BJ; Louie A; Betsch SE 《Radiology》1994,190(3):797
5.
Marcia W. Swanson P.T. Forrest C. Bennett M.D. Kirkwood K. Shy M.D. Michael F. Whitfield M.D. 《Developmental medicine and child neurology》1992,34(4):321-337
The predictive validity of infant neuromotor evaluation by the Movement Assessment of Infants (MAI) was investigated in low-birthweight infants. Motor performance at four and eight months was examined in relation to neurodevelopmental outcome at 18 months of age. Correlations were equally strong between total MAI risk scores at four and eight months and performance on the Bayley Scales. Muscle tone observations were more discriminating at four months, and automatic reactions and volitional movement were most predictive at eight months. The MAI was highly sensitive to neurodevelopmental abnormality at four and eight months and more sensitive than the Bayley Motor Scale; both assessment tools had lower specificity at eight months. The high false-positive rate is attributed to transient neuromotor abnormalities and immaturity of motor function in low-birthweight infants with normal outcome. 相似文献
6.
7.
Brian F O'Donnell Marcia A Wilt Ann Marie Hake Julie C Stout Sandra C Kirkwood Tatiana Foroud 《Movement disorders》2003,18(9):1027-1034
Disturbances of visual cognition, visuomotor performance, and visual memory have been described frequently in Huntington's disease (HD). Early stage visual abnormalities could contribute to these deficits. We evaluated visual processing in 20 control subjects who were non-gene carriers at risk for HD, nine presymptomatic gene-positive subjects, and eight subjects with a recent diagnosis of Huntington's disease. Visual perceptual tests of contrast sensitivity and motion discrimination were used to probe early stage visual processing. Extraocular movements were evaluated in a neurologic examination, and the Digit Symbol test was used to test visual motor performance. Contrast sensitivity did not differ among the three groups. Motion discrimination was impaired in HD subjects but not in the presymptomatic gene carriers when compared to gene noncarriers. Among gene carriers, impaired motion discrimination performance was associated with poorer Digit Symbol performance and extraocular abnormalities. These findings suggest that the early stages of HD are associated with disturbances of motion perception as well as disruptions of visual motor and ocular motor performance. 相似文献
8.
Rupture of the distal biceps tendon: evaluation with MR imaging 总被引:2,自引:0,他引:2
9.
10.
J A Rousou R Kirkwood R M Engelman R H Breyer 《The Journal of thoracic and cardiovascular surgery》1987,93(5):715-718
Postoperative mediastinal effusion after cardiac operations is a common phenomenon and has a potential for serious complications, such as tamponade necessitating urgent drainage. Computed tomography of the chest provides excellent postoperative visualization of the mediastinum. Catheter insertion or paracentesis guided by computed tomography has been used to accomplish nonoperative drainage of symptomatic postoperative mediastinal effusion in six cases. This technique offers simplicity, safety, and cost effectiveness. 相似文献