Abstract:

Our objective was to systematically assess the effect of cytochrome P-450 (CYP450) inhibitors on pharmacokinetics and safety of voriconazole (VORI). Cochrane Library, PubMed, Embase, CNKI, CBM and WanFang databases and Clinicaltrials. gov were searched up to Jan. 26th 2016. Two reviewers independently identified studies, extracted data and assessed quality of studies. Meta-analysis was performed with RevMan 5.3, and risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated. A total of 12 studies were included: three crossover randomized controlled trials, three single-arm before-and-after studies and six cohort studies. Compared with non-combination group, the group of VORI plus omeprazole had a significantly higher occurrence of hepatic dysfunction (RR = 4.11, 95% CI 1.12–15.08, P = 0.03). However, neurologic dysfunction and visual disturbance were not significantly different. Pantoprazole, rabeprazole, cimetidine and contraceptive significantly increased the peak concentration (Cmax) and area under the curve (AUC) of VORI, while indinavir had no significant effect on pharmacokinetics of VORI. The effects of esomeprazole, erythromycin and azithromycin on pharmacokinetic parameters of VORI presented inconsistent results. Co-administration of VORI and CYP450 inhibitors was safe except for omeprazole. Although Cmax and AUC of VORI were increased while co-administered with a couple of CYP450 inhibitors, no significant effect on clinical outcomes was observed.

Key words: Voriconazole, Cytochrome P-450 inhibitors, Systematic review