Abstract:

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), C_min, and C_max 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.

Key words: Voriconazole, Drug-drug interactions, Pharmacokinetics