伏立康唑清除率的患者特异性因素回顾性分析。
A retrospective analysis of patient-specific factors on voriconazole clearance.
作者信息
Dote Satoshi, Sawai Maki, Nozaki Ayumu, Naruhashi Kazumasa, Kobayashi Yuka, Nakanishi Hirokazu
机构信息
Department of Pharmacy, Kyoto-Katsura Hospital, 17 Yamadahirao-cho, Nishikyo-ku, Kyoto 615-8256 Japan.
Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kodo, Kyotanabe-shi, Kyoto 610-0395 Japan.
出版信息
J Pharm Health Care Sci. 2016 Apr 19;2:10. doi: 10.1186/s40780-016-0044-9. eCollection 2016.
BACKGROUND
Voriconazole concentrations display a large variability, which cannot completely be explained by known factors. We investigated the relationships of voriconazole concentration with patient-specific variables and concomitant medication to identify clinical factors affecting voriconazole clearance.
METHODS
A retrospective chart review of voriconazole trough concentration, laboratory data, and concomitant medication in patients was performed. The concentration/dose ratio (C/D-ratio) was assessed as a surrogate marker of total clearance by dividing voriconazole concentration by daily dose per kg of body weight.
RESULTS
A total of 77 samples from 63 patients were obtained. In multiple linear regression analysis, increased C-reactive protein (CRP) level (p < 0.05) and decreased albumin (Alb) level (p < 0.05) were associated with significantly increased C/D-ratio of voriconazole, and coadministration with a glucocorticoid was associated with significantly (p < 0.05) decreased C/D-ratio of voriconazole (adjusted r (2) = 0.31). Regarding CRP and Alb, receiver operating characteristic curve analysis indicated that increased CRP level and decreased Alb level were significant predictors of toxic trough concentration of voriconazole. For CRP, area under the curve (AUC) and cutoff value were 0.71 (95 % confidence interval (CI), 0.57-0.86, p < 0.01) and 4.7 mg/dl, respectively. For Alb, AUC and cutoff value were 0.68 (95 % CI, 0.53-0.82, p < 0.05) and 2.7 g/dl, respectively. A significant difference was seen in voriconazole trough concentration between patients with hepatotoxicity and those without (5.69 μg/ml vs 3.0 μg/ml, p < 0.001).
CONCLUSION
Coadministration of glucocorticoid and inflammation, reflected by elevated CRP level and hypoalbuminemia, are associated with voriconazole clearance. We propose that early measurement of voriconazole concentration before the plateau phase will lead to avoidance of a toxic voriconazole level in patients with elevated CRP level and hypoalbuminemia, although further studies are needed to confirm our findings.
背景
伏立康唑血药浓度存在很大变异性，已知因素无法完全解释这种现象。我们研究了伏立康唑血药浓度与患者个体变量及合并用药之间的关系，以确定影响伏立康唑清除率的临床因素。
方法
对患者的伏立康唑谷浓度、实验室数据及合并用药情况进行回顾性病历审查。通过将伏立康唑浓度除以每千克体重的每日剂量，评估浓度/剂量比（C/D比）作为总清除率的替代指标。
结果
共获得来自63例患者的77份样本。在多元线性回归分析中，C反应蛋白（CRP）水平升高（p < 0.05）和白蛋白（Alb）水平降低（p < 0.05）与伏立康唑C/D比显著升高相关，与糖皮质激素合用与伏立康唑C/D比显著降低（p < 0.05）相关（调整后r² = 0.31）。关于CRP和Alb，受试者工作特征曲线分析表明，CRP水平升高和Alb水平降低是伏立康唑毒性谷浓度的显著预测因素。对于CRP，曲线下面积（AUC）和临界值分别为0.71（95%置信区间（CI），0.57 - 0.86，p < 0.01）和4.7mg/dl。对于Alb，AUC和临界值分别为0.68（95%CI，0.53 - 0.82，p < 0.05）和2.7g/dl。有肝毒性和无肝毒性患者的伏立康唑谷浓度存在显著差异（5.69μg/ml对3.0μg/ml，p < 0.001）。
结论
糖皮质激素的合用以及由CRP水平升高和低白蛋白血症反映的炎症与伏立康唑清除率相关。我们建议在平台期前尽早测定伏立康唑浓度，以避免CRP水平升高和低白蛋白血症患者出现伏立康唑毒性水平，尽管需要进一步研究来证实我们的发现。
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