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目的系统评价泊沙康唑对免疫抑制药药代动力学的影响。方法检索PubMed,EmBase,Cochrane Library,Clinicaltrials.gov,中国知网,万方和中国生物医学文献数据库,纳入比较免疫抑制药联用泊沙康唑前后药代动力学变化的随机对照试验和观察性研究,必要时用RevMan 5.3软件对免疫抑制药药代动力学指标进行Meta分析。结果纳入7篇研究,共258例患者。其中,环孢素2篇共45例患者,他克莫司3篇共62例患者,西罗莫司4篇共151例患者。研究总体质量较差。泊沙康唑与环孢素合用后,环孢素的血药浓度/剂量(C/D)、AUC、Cmax、t1/2分别是合用前的1.38,1.33,1.05,1.21倍;泊沙康唑与他克莫司合用后,他克莫司C/D,AUC,Cmax,t1/2分别是合用前的3.29,4.23,2.14,1.24倍;泊沙康唑与西罗莫司合用后,西罗莫司C/D,AUC,Cmax,t1/2分别是合用前的2.71,8.34,6.37,1.52倍。结论泊沙康唑影响环孢素、他克莫司、西罗莫司的药代动力学参数,为保持有效并安全的血药浓度,合用时,需根据血药浓度减少免疫抑制药的日剂量。 相似文献
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一些新型免疫抑制剂已获准用于临床,另一些正进行临床试验阶段,它们同其他药物合用时可出现一些副作用。他克莫司(FK506)与非甾体抗炎药(NSAID)在药效上相互作用,还有些药物通过改变细胞色素P450活性而显著影响他克莫司的药代动力学,这些均可使他克莫司的肾毒性增加。含氢氧化铝(镁)的抗酸药和考来烯胺可降低麦考酚酸的生物利用度,一些骨髓抑制药物可增加麦考酚酸、西罗莫司和胍立莫司的骨髓毒性。西罗莫司 相似文献
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1病例介绍1.1病例1患者男,45 y,因慢性肾功能不全尿毒症期于2010-06-25日行同种异体肾移植术,术后移植肾功能恢复良好,术后予他克莫司、吗替麦考酚酸酯、强的松治 相似文献
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临床上一些药物与新型免疫抑制剂的相互作用 总被引:3,自引:0,他引:3
一些新型免疫抑制剂已获准用于临床 ,另一些正进行临床试验阶段 ,它们同其他药物合用时可出现一些副作用。他克莫司 (FK50 6)与非甾体抗炎药 (NSAID)在药效上相互作用 ,还有些药物通过改变细胞色素 P450活性而显著影响他克莫司的药代动力学 ,这些均可使他克莫司的肾毒性增加。含氢氧化铝 (镁 )的抗酸药和考来烯胺可降低麦考酚酸的生物利用度 ,一些骨髓抑制药物可增加麦考酚酸、西罗莫司和胍立莫司的骨髓毒性。西罗莫司与环孢素合用时二者血药浓度均上升 ,吲哚美辛则可增加鼠抗 CD3单抗的中枢神经系统副作用 相似文献
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临床药师在查房中发现肾移植患者他克莫司血药浓度过高,分析原因为治疗其真菌感染的伏立康唑抑制了他克莫司的代谢酶细胞色素CYP3A的活性所致。药师由此提出减少他克莫司用量(当他克莫司与伏立康唑联合用药时,他克莫司的剂量调整为原来的1/3)及监测其血药浓度,建议被采纳,患者的他克莫司血药浓度重新达到目标范围。 相似文献
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目的 通过监测造血干细胞移植患者伏立康唑和免疫抑制剂(环孢素A、他克莫司)的稳态血药谷浓度,探讨伏立康唑与环孢素及他克莫司之间的作用。方法 回顾性分析2016年6月-12月于宁波市第一医院血液科住院治疗的造血干细胞移植患者的伏立康唑、环孢素A以及他克莫司的稳态血药浓度数据。结果 伏立康唑与环孢素A合用后,环孢素A稳态谷浓度升高41.55%(P<0.05),伏立康唑稳态谷浓度下降23.31%;伏立康唑与他克莫司合用后,他克莫司稳态谷浓度升高17.52%,伏立康唑稳态谷浓度下降29.45%(P<0.05)。结论 伏立康唑联用环孢素A或他克莫司时,建议诊疗过程严密监测免疫抑制剂及伏立康唑的血药浓度,以便及时调整治疗药物剂量,保障安全、有效、合理用药。 相似文献
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1病例介绍1.1病例1患者男,45 y,因慢性肾功能不全尿毒症期于2010-06-25日行同种异体肾移植术,术后移植肾功能恢复良好,术后予他克莫司、吗替麦考酚酸酯、强的松治 相似文献
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Factors influencing the magnitude and clinical significance of drug interactions between azole antifungals and select immunosuppressants 总被引:6,自引:0,他引:6
The magnitude of drug interactions between azole antifungals and immunosuppressants is drug and patient specific and depends on the potency of the azole inhibitor involved, the resulting plasma concentrations of each drug, the drug formulation, and interpatient variability. Many factors contribute to variability in the magnitude and clinical significance of drug interactions between an immunosuppressant such as cyclosporine, tacrolimus, or sirolimus and an antifungal agent such as ketoconazole, fluconazole, itraconazole, voriconazole, or posaconazole. By bringing similarities and differences among these agents and their potential interactions to clinicians' attention, they can appreciate and apply these findings in a individualized patient approach rather than follow only the one-size-fits-all dosing recommendations suggested in many tertiary references. Differences in metabolism and in the inhibitory potency of cytochrome P450 3A4 and P-glycoprotein influence the onset, magnitude, and resolution of drug interactions and their potential effect on clinical outcomes. Important issues are the route of administration and the decision to preemptively adjust dosages versus intensive monitoring with subsequent dosage adjustments. We provide recommendations for the concomitant use of these agents, including suggestions regarding contraindicated combinations, those best avoided, and those requiring close monitoring of drug dosages and plasma concentrations. 相似文献
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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
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AIMS
Co-administration of standard-dose voriconazole and efavirenz results in a substantial decrease in voriconazole levels, while concurrently increasing efavirenz levels. Hence, concomitant use of standard doses of these drugs was initially contraindicated. This study assessed different dose combinations of efavirenz and voriconazole, with the goal of attaining a dose combination that provides systemic exposures similar to standard-dose monotherapy with each drug.METHODS
This was an open-label, four-treatment, multiple-dose, fixed-sequence study in 16 healthy males. Steady-state pharmacokinetics were assessed following two test treatments (voriconazole 300 mg q12 h + efavirenz 300 mg q24 h and voriconazole 400 mg q12 h + efavirenz 300 mg q24 h) and compared with standard-dose monotherapy (voriconazole 200 mg q12 h or efavirenz 600 mg q24 h).RESULTS
Dose adjustment to voriconazole 300 mg q12 h with efavirenz 300 mg q24 h decreased voriconazole area under the concentration–time curve (AUCτ) and maximum concentration (Cmax), with changes of −55% [90% confidence interval (CI) −62, −45] and −36% (90% CI −49, −21), respectively, when compared with monotherapy. Voriconazole 400 mg q12 h plus efavirenz 300 mg q24 h decreased voriconazole AUCτ (−7%; 90% CI −23, 13) and increased Cmax (23%; 90% CI −1, 53), while increasing efavirenz AUCτ (17%; 90% CI 6, 29) and not changing Cmax when compared with the respective monotherapy regimens. No serious adverse events were observed with voriconazole plus efavirenz.CONCLUSIONS
When co-administered, voriconazole dose should be increased to 400 mg q12 h and efavirenz dose decreased to 300 mg q24 h in order to provide systemic exposures similar to standard-dose monotherapy.WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
- Efavirenz 400 mg q24 h reduces exposure to voriconazole 200 mg q12 h when the two drugs are co-administered.
- Furthermore, voriconazole increases the systemic exposure of efavirenz.
- Co-administration was therefore initially contraindicated.
WHAT THIS STUDY ADDS
- The doses of efavirenz and voriconazole can be adjusted to provide adequate exposure to both drugs when the two are co-administered, without compromising safety.
- Appropriate adjustment of doses for both drugs may thus represent an alternative to a mere contraindication.
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伏立康唑的血药浓度易受CYP2C19基因多态性、药物相互作用、病理生理状态等多种因素影响,个体间呈现明显差异。本文结合国内外文献资料对伏立康唑血药浓度的影响因素进行综述,为临床用药提供参考。 相似文献
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Influence of voriconazole on pharmacokinetics and safety of combined drugs: a systematic review
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We performed a systematic review to evaluate pharmacokinetics changes of drugs when concomitantly used with voriconazole, including randomized controlled trials (RCTs), randomized cross-over trials, self-controlled before-and-after studies, cohort studies and case reports. Literature databases, including Medline, Embase, Cochrane library, were searched to identify eligible studies (until Jan, 2016). A modified risk of bias tool specially developed in this research was used to evaluate the quality of pharmacokinetic randomized crossover trials and self-controlled before-and-after studies. Cochrane risk of bias tool provided by Cochrane Library and Cochrane Reviewer’s handbook was used to evaluate the quality of RCTs and non-randomized controlled studies. Pharmacokinetic parameters, such as area under curve (AUC), Cmin, and Cmax before and after using voriconalzole were collected. Meta-analysis was conducted to synthesize results if possible. Among 41 studies included in our search, 17 were randomized crossover trials, 3 were RCTs, 13 were self-controlled before-and-after study (SBAs), 1 was cohort studies and 7 were case reports. A total of 12 classes of drugs were involved, including opiates, non-steroidal anti-inflammatory drugs (NSAIDs), psychopathic drugs, anti-HIV drugs, immunosuppressors, oral contraceptive, digoxin, warfarin, oral hypoglycemic agents, antihypertensive agents, lipid regulating agents and cytotoxic agents. According to our results, the impacts of voriconazole on tilidine, buprenorphine, etoricoxib, meloxicam, venlafaxine, midazolam, zolpidem, etravirine and sirolimus were different from the package insert. Our systematic review provided comprehensive data on the pharmacokinetics changes of drugs when used in combination with voriconazole. 相似文献
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The possible clinical impact of risperidone on P‐glycoprotein‐mediated transport of tacrolimus: A case report and in vitro study
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Nao Watanabe Hiroki Higashi Saki Nakamura Keiko Nomura Yuichi Adachi Masato Taguchi 《Biopharmaceutics & drug disposition》2018,39(1):30-37
The authors encountered the case of an 8‐fold increase in the concentration/dose (C/D) ratio of tacrolimus (TAC) following the coadministration of voriconazole (VRCZ) in a hematopoietic stem cell transplantation (HSCT) recipient. The interaction observed was much greater than expected and the patient had also been treated with oral risperidone (RSP). It was hypothesized that cytochrome P450 (CYP)3A inhibition of the small intestine by voriconazole and P‐glycoprotein (P‐gp) inhibition of the small intestine by risperidone exerted a synergistic effect on the bioavailability of tacrolimus. The aim of the present study was to evaluate the effect of risperidone on the P‐gp‐mediated transport of tacrolimus. The transcellular transport of P‐gp substrates was examined in Caco‐2 and P‐gp‐expressing renal epithelial LLC‐GA5‐COL150 cells. In Caco‐2 cells, the apical‐basal (A‐B) transport of rhodamine123 (Rh123) after a 120 min incubation was increased by 47.1%, whereas that in the B‐A direction was decreased by 61.7% in the presence of risperidone (100 μm ). These results indicate that risperidone showed an inhibitory effect on the P‐gp‐mediated transport of Rh123. In LLC‐GA5‐COL150 cells, the A‐B transport of tacrolimus after 120 min incubation was increased by 21.7% in the presence of risperidone (100 μm ), whereas that in the B‐A direction was decreased by 10.7%. These results suggest that risperidone was at least partly involved in the mechanism of the marked increase in the C/D ratio of tacrolimus. This case report provides new insights into the diversity of drug interactions of tacrolimus triggered by the combination of two concomitant drugs. 相似文献
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程军 《中国医院药学杂志》2019,39(23):2428-2431
目的:分析伏立康唑致骨膜炎(voriconazole-induced periostitis,VIP)的发生规律及特点,为安全用药提供参考。方法:以"伏立康唑"和"骨膜炎"与"voriconazole"和"periostitis"为检索词,检索伏立康唑上市后CNKI、VIP、Wanfang及PubMed数据库收载的伏立康唑致骨膜炎病例个案报道,并进行分析。结果:共筛选出有效个案报道32篇,45例患者,男19例,女26例。使用伏立康唑6月后出现骨膜炎31例(68.9%)。临床表现主要为弥漫性骨痛。患者停止使用伏立康唑后,弥漫性骨痛症状消失。结论:骨膜炎是长期使用伏立康唑的可逆性不良反应,应加强用药监测,以便及时发现和处理骨膜炎。 相似文献
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目的探讨伏立康唑与血液病患者常用药间的药物相互作用,指导伏立康唑个体化用药。方法收集2015-2017年天津市第一中心医院应用伏立康唑预防或治疗侵袭性真菌感染的血液病患者的血药浓度资料,应用非线性混合效应模型法,考察血液病患者常用药物与伏立康唑联用时的相互作用。结果伏立康唑清除率和表观分布容积的群体典型值分别为8.24 L·h^-1和163 L。群体药动学模型显示碱性磷酸酶对伏立康唑的清除率有显著影响(P<0.005)。联用兰索拉唑或环孢素时,伏立康唑的清除率分别降低33.4%、32.8%,而联用地塞米松使伏立康唑的清除率增加41.0%。结论临床上伏立康唑与兰索拉唑、环孢素或地塞米松联用时,需注意相互作用的产生,并合理调整用药剂量。 相似文献