Effect of cytochrome P450 2C19 polymorphisms on the clinical outcomes of voriconazole: a systematic review and meta-analysis.

BACKGROUND: Genetic polymorphisms of cytochrome P450 enzymes, especially CYP2C19, could influence voriconazole pharmacokinetics. The association between CYP2C19 polymorphisms and voriconazole clinical outcomes is not well established. The aim of this meta-analysis was to evaluate the effect of CYP2C19 polymorphisms on clinical outcomes in patients treated with voriconazole.

METHODS: PubMed, EMBASE, CENTRAL, ClinicalTrials.gov, and three Chinese databases were searched from their inception to January 2016 to identify eligible trials that reported voriconazole exposure and clinical outcomes of voriconazole according to CYP2C19 polymorphisms. Two reviewers independently reviewed the citations, extracted the data, and assessed the quality of the trials. The meta-analysis was performed using RevMan5.3.

RESULTS: A total of ten studies involving 598 patients were included. Compared with patients with extensive metabolizer (EM) phenotype, patients with poor metabolizer (PM) phenotype had significantly higher trough concentrations (MD, 1.22 mg/L; 95 % confidence interval (CI), 0.72-1.71; P < 0.0001). PM phenotype was also associated with a higher treatment success rate compared with EM phenotype (risk ratio (RR), 1.31; 95 % CI, 1.04-1.67; P = 0.02). However, there was no significant association between CYP2C19 polymorphisms and daily maintenance dose, overall adverse events, hepatotoxicity, and neurotoxicity.

CONCLUSIONS: Patients with CYP2C19 PM phenotype were associated with increased treatment success rate and trough concentrations as compared with those with EM phenotype. There was no significant association between CYP2C19 polymorphisms and either daily maintenance dose or adverse outcomes of voriconazole. However, large-scale, high-quality trials are still needed to confirm these findings.