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排序方式: 共有152条查询结果,搜索用时 31 毫秒
101.
102.
Mladen V. Tzvetkov Joao N. dos Santos Pereira Ingolf Meineke Ali R. Saadatmand Julia C. Stingl Jürgen Brockmöller 《Biochemical pharmacology》2013
We investigated whether morphine and its pro-drug codeine are substrates of the highly genetically polymorphic organic cation transporter OCT1 and whether OCT1 polymorphisms may affect morphine and codeine pharmacokinetics in humans. 相似文献
103.
104.
Kaidi Zhou Jibran Y. Khokhar Bin Zhao Rachel F. Tyndale 《Biochemical pharmacology》2013,85(12):1848-1855
The response to centrally acting drugs is highly variable between individuals and does not always correlate with plasma drug levels. Drug-metabolizing CYP enzymes in the brain may contribute to this variability by affecting local drug and metabolite concentrations. CYP2D metabolizes codeine to the active morphine metabolite. We investigated the effect of inhibiting brain, and not liver, CYP2D activity on codeine-induced analgesia. Rats received intracerebroventricular injections of CYP2D inhibitors (20 μg propranolol or 40 μg propafenone) or vehicle controls. Compared to vehicle-pretreated rats, inhibitor-pretreated rats had: (a) lower analgesia in the tail-flick test (p < 0.05) and lower areas under the analgesia-time curve (p < 0.02) within the first hour after 30 mg/kg subcutaneous codeine, (b) lower morphine concentrations and morphine to codeine ratios in the brain (p < 0.02 and p < 0.05, respectively), but not in plasma (p > 0.6 and p > 0.7, respectively), tested at 30 min after 30 mg/kg subcutaneous codeine, and (c) lower morphine formation from codeine ex vivo by brain membranes (p < 0.04), but not by liver microsomes (p > 0.9). Analgesia trended toward a correlation with brain morphine concentrations (p = 0.07) and correlated with brain morphine to codeine ratios (p < 0.005), but not with plasma morphine concentrations (p > 0.8) or plasma morphine to codeine ratios (p > 0.8). Our findings suggest that brain CYP2D affects brain morphine levels after peripheral codeine administration, and may thereby alter codeine's therapeutic efficacy, side-effect profile and abuse liability. Brain CYPs are highly variable due to genetics, environmental factors and age, and may therefore contribute to interindividual variation in the response to centrally acting drugs. 相似文献
105.
LC-MS/MS法测定比格犬血浆中的磷酸可待因 总被引:1,自引:0,他引:1
目的建立灵敏、快速的LC-MS/MS法测定比格犬血浆中磷酸可待因浓度的方法。方法血浆样品经乙醚-二氯甲烷(60∶40)萃取后,以甲酸-10 mmol·L-1乙酸-甲醇(0.2∶62∶38)为流动相,盐酸利多卡因为内标,采用Phenomenex C18(150 mm×2 mm,3μm)色谱柱进行分离,流速0.2 mL·min-1,进样量10μL;LC-MS/MS法选择反应监测方式,定量分析的离子反应分别为m/z 300→165(磷酸可待因)和m/z 235→86(盐酸利多卡因)。结果 0.08~16 ng·mL-1磷酸可待因与峰面积的线性关系良好(r=0.9977);其最低定量下限为0.08 ng·mL-1,绝对回收率大于85%,批间和批内的变异系数小于15%。结论所用方法操作简便、快速、选择性好、灵敏度高,适用于磷酸可待因的生物等效性及药物动力学的研究。 相似文献
106.
Eshtehardi P Ghassemi-Kakroodi P Garachemani A Eslami M Moayed DA 《Heart & lung : the journal of critical care》2011,40(4):e112-e114
We report on a 20-year-old man who presented with an extensive acute anteroseptal myocardial infarction (from a thrombotic occlusion of the left anterior coronary artery) as the initial manifestation of hereditary protein C deficiency. This case report, along with previous reports, indicates that a diagnosis of protein C deficiency in young patients with myocardial infarctions is essential for more appropriate management and for the prevention of recurrent events. Furthermore, family screening could lead to a prophylactic approach in carriers of this mutation. 相似文献
107.
Stacy S. Shord Larisa H. Cavallari Weihua Gao Hyun-Young Jeong Kelly Deyo Shitalben R. Patel Joseph R. Camp Susan M. Labott Robert E. Molokie 《European journal of clinical pharmacology》2009,65(7):651-658
Purpose We conducted a prospective, open-label study in 54 adult subjects with sickle cell disease to determine the relationship between
morphine concentrations, cytochrome P450 (CYP) 2D6 genotype, and clinical outcomes.
Methods A blood sample was obtained for genotyping and serial blood samples were drawn to measure codeine and its metabolites in the
plasma before and after oral codeine sulfate 30mg. Codeine and its metabolites were measured by liquid chromatography-tandem
mass spectrometry (LC-MS). CYP2D6 genetic testing included four single nucleotide polymorphisms (SNP) indicative of three variant alleles: *17 (1023T); *29
(1659A, 3183A); and *41 (2988A) alleles.
Results Thirty subjects (group I) had a mean (standard deviation) maximal morphine concentration of 2.0 (1.0) ng/ml. Morphine was
not measurable in the remaining 24 subjects (group II). Nine (30%) subjects in group I and 11 (46%) subjects in group II carried
a variant *17, *29, or *41 allele (p = 0.23); one (3%) subject in group I and 5 (21%) subjects in group II were homozygous
for *17 or *29 allele (p = 0.07). Emergency room visits (group I 1.5 ± 1.8 vs. group II 2.1 ± 4.3, p = NS) did not differ
based on metabolic status, but more hospital admissions (0.9 ± 1.4 vs. 2.2 ± 4.1, p = 0.05) were documented in patients with
no measurable morphine concentrations.
Conclusions We conclude that Blacks with sickle cell disease without measurable plasma morphine levels after a single dose of codeine
were not more likely to be a carrier of a single variant allele commonly associated with reduced CYP2D6 metabolic capacity;
however, homozygosity for a variant CYP2D6 allele may result in reduced metabolic capacity. Furthermore, it appears that subjects without measurable morphine concentrations
were more likely to be admitted to the hospital for an acute pain crisis.
This study was supported in part by the Illinois Department of Public Health awarded to the Sickle Cell Center, Janssen Medical
Affairs, LLC (FEN-EMR4007) and a Clinical Translational Science Award from the Center for Clinical Translational Science at
the University of Illinois awarded to Dr. Stacy S. Shord and the General Clinical Research Center at the University of Illinois
Medical Center at Chicago (NIH grant M01-RR-13987). 相似文献
108.
《European annals of otorhinolaryngology, head and neck diseases》2014,131(4):233-238
The authors present the guidelines of the French Oto-rhino-laryngology – Head and Neck Surgery Society (SFORL) regarding pain management in children and adults following tonsillectomy. A multidisciplinary work group was entrusted with a literature review. Guidelines were drawn up based on the articles retrieved and the group members’ experience. They were read over by an editorial group independent of the work group. A coordination meeting drew up the final version. Guidelines were graded A, B or C or as professional agreement in decreasing order of level of evidence. At home, non-steroid anti-inflammatory drugs (NSAIDs) are recommended in association with paracetamol in elevated respiratory risk and especially obstructive sleep apnea syndrome; in elevated hemorrhagic risk (hemostasis disorder, surgical problems, etc.), tramadol is recommended. Two other treatment schedules (modified NSAIDs and corticosteroids) have not undergone dedicated study and should be assessed. Management of post-tonsillectomy pain in children is founded on individual risk/benefit analysis. 相似文献
109.
目的 提高强力枇杷露的质量标准.采用高效液相色谱法对强力枇杷露中的吗啡与可待因进行含量的同时测定.方法 色谱柱为Agilent Eclipse C18色谱柱(4.6 mm×250 mm,5μm),以乙腈-0.01 mol·L-1磷酸二氢钾-磷酸-三乙胺溶液(5∶95∶0.2∶0.4)为流动相,流速1.0 mL·min-1,检测波长220 nm.结果 吗啡的进样量在0.229 3~4.586 μg范围内呈良好的线性关系(r=0.999 2),平均加样回收率为100.35%,RSD为2.87%(n=6);可待因的进样量在0.037 11~0.741 1μg范围内呈良好的线性关系(r=0.999 9),平均加样回收率为106.78%,RSD为2.09%(n=6).结论 方法经济合理、简便准确,可用于强力枇杷露中吗啡和可待因的含量测定. 相似文献
110.
It has been shown that the association of non‐steroidal anti‐inflammatory drugs (NSAIDs) with opioid analgesic agents can increase their antinociceptive activity, allowing the use of lower doses and thus limiting side effects. Therefore, the aim of the present study was to examine the possible pharmacological interaction between lumiracoxib and codeine or nalbuphine at the local peripheral level in the rat using the 1% formalin test and isobolographic analysis. Lumiracoxib, codeine, nalbuphine or fixed‐dose ratios lumiracoxib—codeine or lumiracoxib—nalbuphine combinations were administrated locally in the formalin‐injured paw and the antinociceptive effect was evaluated using the 1% formalin test. All treatments produced a dose‐dependent antinociceptive effect. ED40 values were estimated for the individual drugs and an isobologram was constructed. The derived theoretical ED40's for the lumiracoxib—codeine and lumiracoxib—nalbuphine combinations were 423.4±31.3μg/paw and 310.9±24.2μg/paw, respectively, being significantly higher than the actually observed experimental ED40 values, 233.2±30.9μg/paw and 132.7±11.6μg/paw, respectively. These results correspond to a synergistic interaction between lumiracoxib and opioids at the local peripheral level, potency being about two times higher with regard to that expected from the addition of the effects of the individual drugs. Data suggest that low doses of the lumiracoxib—opioids combination can interact synergistically at the peripheral level and therefore this drug association may represent a therapeutic advantage for the clinical treatment of inflammatory pain. 相似文献