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A retrospective analysis of patient-specific factors on voriconazole clearance.

Dote S, Sawai M, Nozaki A, Naruhashi K, Kobayashi Y, Nakanishi H - J Pharm Health Care Sci (2016)

Bottom Line: 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.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).Coadministration of glucocorticoid and inflammation, reflected by elevated CRP level and hypoalbuminemia, are associated with voriconazole clearance.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Kyoto-Katsura Hospital, 17 Yamadahirao-cho, Nishikyo-ku, Kyoto 615-8256 Japan.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Receiver operating characteristic (ROC) curves for predicting risk of toxic voriconazole level on the basis of CRP (a) and Alb (b); relationships of toxic voriconazole level with CRP and Alb (c). The true-positive rate represents the proportion of true positives that are correctly classified as positive. The false-positive rate represents the proportion of true negatives that are incorrectly classified as positive. True-positive rate = true positives/(true positives + false negatives). False-positive rate = false positives/(false positives + true negatives). Closed circles represent patients with toxic voriconazole level and open circles represent patients without toxic voriconazole level. 95 % CI, 95 % confidence interval
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Fig3: Receiver operating characteristic (ROC) curves for predicting risk of toxic voriconazole level on the basis of CRP (a) and Alb (b); relationships of toxic voriconazole level with CRP and Alb (c). The true-positive rate represents the proportion of true positives that are correctly classified as positive. The false-positive rate represents the proportion of true negatives that are incorrectly classified as positive. True-positive rate = true positives/(true positives + false negatives). False-positive rate = false positives/(false positives + true negatives). Closed circles represent patients with toxic voriconazole level and open circles represent patients without toxic voriconazole level. 95 % CI, 95 % confidence interval

Mentions: Multiple linear regression analysis indicated that CRP and Alb were the factors affecting voriconazole clearance. ROC curve analysis indicated that increased CRP level and decreased Alb level were significant predictors of toxic trough concentration of voriconazole: A) CRP - area under the curve (AUC) 0.71 (95 % confidence interval [CI], 0.57–0.86, p < 0.01), cutoff value 4.7 mg/dl (sensitivity 60.9 %, specificity 82.7 %); B) Alb - AUC 0.68 (95 % CI, 0.53–0.82, p < 0.05), cutoff value 2.7 g/dl (sensitivity 61.9 %, specificity 73.7 %) (Fig. 3).Fig. 3


A retrospective analysis of patient-specific factors on voriconazole clearance.

Dote S, Sawai M, Nozaki A, Naruhashi K, Kobayashi Y, Nakanishi H - J Pharm Health Care Sci (2016)

Receiver operating characteristic (ROC) curves for predicting risk of toxic voriconazole level on the basis of CRP (a) and Alb (b); relationships of toxic voriconazole level with CRP and Alb (c). The true-positive rate represents the proportion of true positives that are correctly classified as positive. The false-positive rate represents the proportion of true negatives that are incorrectly classified as positive. True-positive rate = true positives/(true positives + false negatives). False-positive rate = false positives/(false positives + true negatives). Closed circles represent patients with toxic voriconazole level and open circles represent patients without toxic voriconazole level. 95 % CI, 95 % confidence interval
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4835838&req=5

Fig3: Receiver operating characteristic (ROC) curves for predicting risk of toxic voriconazole level on the basis of CRP (a) and Alb (b); relationships of toxic voriconazole level with CRP and Alb (c). The true-positive rate represents the proportion of true positives that are correctly classified as positive. The false-positive rate represents the proportion of true negatives that are incorrectly classified as positive. True-positive rate = true positives/(true positives + false negatives). False-positive rate = false positives/(false positives + true negatives). Closed circles represent patients with toxic voriconazole level and open circles represent patients without toxic voriconazole level. 95 % CI, 95 % confidence interval
Mentions: Multiple linear regression analysis indicated that CRP and Alb were the factors affecting voriconazole clearance. ROC curve analysis indicated that increased CRP level and decreased Alb level were significant predictors of toxic trough concentration of voriconazole: A) CRP - area under the curve (AUC) 0.71 (95 % confidence interval [CI], 0.57–0.86, p < 0.01), cutoff value 4.7 mg/dl (sensitivity 60.9 %, specificity 82.7 %); B) Alb - AUC 0.68 (95 % CI, 0.53–0.82, p < 0.05), cutoff value 2.7 g/dl (sensitivity 61.9 %, specificity 73.7 %) (Fig. 3).Fig. 3

Bottom Line: 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.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).Coadministration of glucocorticoid and inflammation, reflected by elevated CRP level and hypoalbuminemia, are associated with voriconazole clearance.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, Kyoto-Katsura Hospital, 17 Yamadahirao-cho, Nishikyo-ku, Kyoto 615-8256 Japan.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus