摘要
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.
通过纳入随机对照试验、随机交叉试验、自身前后对照研究、队列研究和病例报告,评价伏立康唑对联合使用药物的药代动力学参数和安全性的影响。系统检索Pub Med、Embase、Cochrane Library、Clinicaltrials.gov、中国知网、万方和中国生物医学文献数据库,检索时间从建库至2016年1月。本文采用改良的偏倚风险工具评价药代动力学随机交叉研究和自身前后对照研究的质量,用Cochrane Library和Cochrane Reviewer’s handbook中的偏倚风险工具评价随机对照试验研究和非随机对照试验研究的质量。提取药物与伏立康唑联合使用前后,药物的曲线下面积(AUC),血药谷浓度(C_(min))和峰浓度(C_(max))等药代动力学参数及安全性数据(Safety)。必要时,用荟萃分析合并结果。总共纳入了41篇研究,包括17篇随机交叉试验,3篇随机对照试验,13篇自身前后对照研究,1篇队列研究和7篇病例报告。研究中评价了伏立康唑对12类药物的影响,包括阿片类镇痛药、抗精神病药、抗艾滋病药、免疫抑制剂、口服避孕药、地高辛、华法林、口服降糖药、降压药、降脂药和细胞毒化疗药。根据本研究的结果,伏立康唑对替利定、丁丙诺啡、依托考昔、美洛昔康、文拉法辛、咪达唑仑、唑吡坦、依曲韦林和西罗莫司的影响与伏立康唑说明书不一致。本系统评价展示了伏立康唑对联合使用药物的药代动力学参数和安全性的影响。
