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461.
目的 探讨临床药师参与药学实践对促进临床合理用药的作用.方法 临床药师通过建议监测肺曲霉菌感染合并癫痫患者静脉序贯口服伏立康唑后的血药浓度,予以增加剂量和检测相关代谢酶的基因多态性,并分析抗感染疗效不佳的原因,参与临床治疗.结果 第1次监测时伏立康唑体内血药浓度较低,临床药师建议将剂量加倍后仍较低;考虑受CYP2C19... 相似文献
462.
Andrews E Damle BD Fang A Foster G Crownover P LaBadie R Glue P 《British journal of clinical pharmacology》2008,65(4):531-539
AIM
To assess the two-way pharmacokinetic interaction between voriconazole and Ortho-Novum® 1/35, an oral contraceptive containing norethindrone 1 mg and ethinyl oestradiol 35 μg.METHODS
In this open-label, three-period, fixed-sequence study, 16 healthy females received voriconazole (400 mg q12 h, day 1; 200 mg q12 h, days 2–4) (period 1), oral contraceptive (q24 h, days 12–32) (period 2), and combination voriconazole (400 mg q12 h, day 57; 200 mg q12 h, days 58–60) and oral contraceptive (q24 h, days 40–60) (period 3).RESULTS
Voriconazole geometric mean AUCτ and Cmax increased 46% (12 682–18 495 ng h ml−1; 90% confidence interval [CI] 32, 61) and 14% (2485–2840 ng ml−1; 90% CI 3, 27), respectively, when co-administered with oral contraceptive vs. voriconazole alone. Ethinyl oestradiol geometric mean AUCτ and Cmax increased 61% (1031–1657 ng h ml−1; 90% CI 50, 72) and 36% (119–161 ng ml−1; 90% CI 28, 45), respectively, and norethindrone geometric mean AUCτ and Cmax increased 53% (116–177 ng h ml−1; 90% CI 44, 64) and 15% (18–20 ng ml−1; 90% CI 3, 28), respectively, during voriconazole co-administration vs. oral contraceptive alone. Neither ethinyl oestradiol nor norethindrone levels were reduced in subjects following voriconazole co-administration. Adverse events (AEs) were generally mild, occurring less in subjects receiving voriconazole alone (36 events) vs. oral contraceptive alone (88 events) or combination treatment (68 events); four subjects experienced a severe AE.CONCLUSIONS
Co-administration of voriconazole and oral contraceptive increased systemic exposures of all analytes relative to respective monotherapy. Although generally safe and well tolerated, it is recommended that patients receiving co-administered voriconazole and oral contraceptive be monitored for development of AEs commonly associated with these medications.WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
- Voriconazole, a broad-spectrum antifungal drug, is a substrate and inhibitor of CYP2C19 and CYP3A4 isozymes.
- Ethinyl oestradiol and norethindrone, components of the combination oral contraceptive drug Ortho-Novum® 1/35, also are substrates of cytochrome P450 CYP2C19 and CYP3A4 isozymes.
- Because co-administration of voriconazole and Ortho-Novum® 1/35 could potentially result in pharmacokinetic interactions that increase systemic exposure of one or both drugs to unsafe levels, clinical studies are needed to define better the two-way pharmacokinetic interaction between these drugs.
WHAT THIS STUDY ADDS
- Although co-administered voriconazole and oral contraceptive did result in increased systemic exposures of all three drugs relative to respective monotherapy, co-administered treatment was generally safe and well tolerated.
- It is recommended, however, that patients receiving co-administered voriconazole and oral contraceptives be monitored for the development of adverse events commonly associated with these medications.
463.
2-氟丙酰乙酸乙酯(1)是抗真菌药伏立康唑(voriconazole)的中间体,可用氟乙酸乙酯与丙酰氯在氢化钠作用下反应制得,收率21%;也可用溴代氟乙酸乙酯与ylide试剂反应后再经丙酰氯酰化、水解得到,收率50%。前者反应剧烈、不易控制;后者操作复杂,条件苛刻。 相似文献
464.
1例75岁男性患者既往没有使用过多潘立酮,既往无心律不齐病史,患者于2015年9月17开始使用多潘立酮片10 mg tid以促进胃肠动力,避免反流。9月21日,尿培养结果提示克柔念珠菌,考虑不除外真菌感染,加用伏立康唑,当日患者出现心律加快,律不齐,25日停用伏立康唑,未停用多潘立酮。直至患者出院(9月30日),患者心律不齐未缓解。判断该患者出现心律不齐是多潘立酮导致的不良反应的关联性评价为可能。多潘立酮主要通过CYP3A4酶代谢,而伏立康唑为CYP3A4酶的强抑制剂,两者合用会降低多潘立酮的代谢,从而增加多潘立酮的浓度。该例患者合用伏立康唑以后,出现心律失常,考虑为伏立康唑导致多潘立酮血药浓度增高或两种药物的心脏不良反应叠加所致。 相似文献
465.
目的建立一种快速、灵敏的高效液相色谱法测定人血浆中伏立康唑浓度。方法采用氯仿进行血浆样品萃取,采用高效液相色谱-紫外检测法测定。色谱柱:Diamonsil C18柱(200 mm×4.6 mm,5μm),流动相:0.01 mol.L-1醋酸铵(加冰醋酸、三乙胺各10μL)-乙腈(50∶50),紫外检测波长:255 nm。结果伏立康唑回收率>90%,浓度在0.03~8.80μg.mL-1,伏立康唑和酮康唑的峰面积比与伏立康唑浓度间呈现良好的线性关系(r2=0.999 71),日内和日间RSD均<15%。结论该方法快速、灵敏,适合于伏立康唑的临床血药浓度监测及药动学研究。 相似文献
466.
S. Kamachi K. Sugimoto T. Yamasaki N. Hirose H. Ide Y. Ohyama 《Xenobiotica; the fate of foreign compounds in biological systems》2013,43(10):701-712
1. 1α -Hydroxyvitamin D 3 (1 α-OH-D 3) is a synthetic prodrug of the active form of vitamin D 3, and requires the hydroxylation at the C-25 position before eliciting its biological activity. 2. 25-Hydroxylation activities for 1 α-OH-D 3 were present in both microsomal and mitochondrial fractions of human liver. 3. To determine the P450 enzyme(s) involved in microsomal 25-hydroxylation, 14 P450s (CYP1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9-Arg, 2C9-Cys, 2C19, 2D6-Val, 2D6- Met, 2E1, 3A4, 4A11) were tested for their 25-hydroxylation activity of 1 α-OH-D 3. None catalysed the 25-hydroxylation reaction. 4. 1 α-OH-D 3 in a high concentration (2.5 ng ml -1) showed small but significant inhibition of the catalytic activities of CYP2C8, 2C9-Cys, 2C19, 2D6-Val and 2E1 for their typical substrates. However, 1 α-OH-D 3 in a clinically used low concentration will not significantly affect drug metabolism catalysed by the 14 P450s tested. 5. In summary, the 25-hydroxylation activity of 1 α-OH-D 3 that localizes in the microsomal fraction appears to be attributable to a cytochrome P450 other than the microsomal forms tested in this study. 相似文献
467.
在2例恶性血液病合并真菌感染患者的治疗中发现,环孢素与伏立康唑联用导致环孢素血药浓度升高,引起高血钾症。在治疗过程中应减少环孢素给药剂量并监测其血药浓度,根据监测结果及时调整剂量。 相似文献
468.
目的:分别建立超滤法和溶剂萃取法处理样品,结合高效液相色谱(HPLC)法测定人血浆中伏立康唑游离型药物浓度Cu和总血药浓度Ct,并计算蛋白结合率。方法:游离型药物浓度采用Millipore Centrifree超滤装置前处理,以外标法测定;总血药浓度测定采用内标法,经蛋白沉淀、溶剂萃取、复溶后测定。结果:游离型药物浓度和总血药浓度的线性范围分别为0.20~12.64 μg·mL-1和0.02~10.24 μg·mL-1;游离型药物浓度和总血药浓度的准确度和精密度均在±15%范围内,ICU患者的伏立康唑血浆蛋白结合率为42.4%。结论:本方法前处理方法便捷,选择性强,准确度高,可用于人血浆中伏立康唑蛋白结合率的测定。 相似文献
469.
470.
伏立康唑与奥美拉唑可能的不良相互作用致肌病及肝功能恶化 总被引:4,自引:0,他引:4
1例35岁男性患者,因慢性重型乙型肝炎并自发性腹膜炎入院,给予保肝、退黄、利尿、抑酸(奥美拉唑)和抗病毒(阿德福韦酯+拉米夫定)药物治疗,其间发生肺部侵袭性真菌感染。给予卡泊芬净抗真菌治疗10 d,实验室检查结果及临床症状好转。后因经济原因改为口服伏立康唑(首剂量0.4 g,之后0.2 g2,次/d),治疗第3天患者开始出现频繁的恶心、呕吐,对症治疗效果不佳;第10天改为伏立康唑0.2 g、2次/d静脉滴注,仍频繁呕吐;治疗第14天出现四肢肌肉酸痛症状,实验室检查示:AST880 U/L,ALT 166 U/L,CK 22 855 U/L and CK-MB 442 U/L。停用伏立康唑4,d后患者CK和CK-MB水平分别降至5625 U/L和73 U/L,但AST和ALT水平分别升至1226 U/L和396 U/L。该肌病和肝功能恶化考虑可能与伏立康唑和奥美拉唑不良相互作用有关。患者最终肝衰竭,家属主动要求出院。 相似文献