Investigation and threshold of optimum blood concentration of voriconazole: a descriptive statistical meta-analysis.
Voriconazole (VRCZ) reportedly possesses a broad spectrum of antifungal activity against Aspergillus spp. and Candida spp., and the blood concentration of VRCZ is correlated with both the efficacy and the adverse effects of this drug. Monitoring of the blood concentration target level of VRCZ has not yet been widely adopted in the medical field, and no evidence concerning this target level has been reported. Accordingly, we used a meta-analysis to investigate the optimal blood concentration of VRCZ. Using data from 12 reports, we found that the success rate for fungal infection treatment increased significantly at VRCZ levels greater than 1.0 μg/ml when a graded cutoff value within the range of 1.0-3.0 μg/ml was used as the VRCZ trough blood concentration [odds ratio (OR) 7.23, 95% confidence interval (CI) 2.84-18.37, P < 0.0001]. Concerning the safety evaluation, the incidence of adverse neurological effects increased significantly at a cutoff value of 4.0 μg/ml when a graded cutoff value within the range of 3.0-6.0 μg/ml was used (OR 2.23, 95% CI 1.12-4.46, P = 0.02). However, in all 12 literature sources, an increasing incidence of liver dysfunction was reported at higher blood concentrations, and no accurate cutoff values were obtained. Consequently, a VRCZ trough blood concentration more than 1.0 μg/ml from the perspective of efficacy and less than 4.0 μg/ml from the perspective of safety is recommended.
Department of Pharmacy, Kitasato University East Hospital, 2-1-1, Asamizodai, Minamiku, Sagamihara, Kanagawa, 258-0380, Japan. yuki@kitasato-u.ac.jp
Yukihiro
Y
Hamada
Yoshinori
Y
Seto
Kazuo
K
Yago
Masakazu
M
Kuroyama
D000367:Age Factors; D000935:Antifungal Agents / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D008107:Liver Diseases / Q000097:blood; D008297:Male; D009181:Mycoses / Q000097:blood / Q000188:drug therapy; D016017:Odds Ratio; D011743:Pyrimidines / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D014230:Triazoles / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use; D065819:Voriconazole
D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole