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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

Relationship between voriconazole dosages per patient weight and voriconazole trough concentration. Each point represents a measurement. The linear regression curve is presented with coefficient of determination (r2)
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Fig1: Relationship between voriconazole dosages per patient weight and voriconazole trough concentration. Each point represents a measurement. The linear regression curve is presented with coefficient of determination (r2)

Mentions: Significant correlation was found between administered dosage and trough concentration of voriconazole (r2 = 0.14, p < 0.001), (Fig. 1). Mean (SD) C/D-ratio significantly decreased from 0.66 (0.42) to 0.43 (0.33) by concomitant administration with glucocorticoid (p = 0.01) (Fig. 2). Effect of concomitant macrolide on C/D-ratio was not conducted because only two patients was administered erythromycin. Significant correlations were found between C/D-ratio of voriconazole and Alb (r2 = 0.16, p < 0.01), CRP (r2 = 0.26, p < 0.0001). Alb, CRP, and age (p = 0.07) were treated as continuous variables and glucocorticoid use was treated as a dichotomous variable in multiple linear regression analysis. Increased CRP level and decreased Alb level were significantly associated with increased C/D-ratio of voriconazole, and coadministration with a glucocorticoid was significantly associated with decreased C/D-ratio of voriconazole (adjusted r2 = 0.31) (Table 2). We did a post-hoc analysis of the effect of coadministration with a glucocorticoid on interpatient variability of voriconazole concentration in three patients (Table 3). C/D-ratio was considerably decreased by glucocorticoid administration in all three patients.Fig. 1


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)

Relationship between voriconazole dosages per patient weight and voriconazole trough concentration. Each point represents a measurement. The linear regression curve is presented with coefficient of determination (r2)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig1: Relationship between voriconazole dosages per patient weight and voriconazole trough concentration. Each point represents a measurement. The linear regression curve is presented with coefficient of determination (r2)
Mentions: Significant correlation was found between administered dosage and trough concentration of voriconazole (r2 = 0.14, p < 0.001), (Fig. 1). Mean (SD) C/D-ratio significantly decreased from 0.66 (0.42) to 0.43 (0.33) by concomitant administration with glucocorticoid (p = 0.01) (Fig. 2). Effect of concomitant macrolide on C/D-ratio was not conducted because only two patients was administered erythromycin. Significant correlations were found between C/D-ratio of voriconazole and Alb (r2 = 0.16, p < 0.01), CRP (r2 = 0.26, p < 0.0001). Alb, CRP, and age (p = 0.07) were treated as continuous variables and glucocorticoid use was treated as a dichotomous variable in multiple linear regression analysis. Increased CRP level and decreased Alb level were significantly associated with increased C/D-ratio of voriconazole, and coadministration with a glucocorticoid was significantly associated with decreased C/D-ratio of voriconazole (adjusted r2 = 0.31) (Table 2). We did a post-hoc analysis of the effect of coadministration with a glucocorticoid on interpatient variability of voriconazole concentration in three patients (Table 3). C/D-ratio was considerably decreased by glucocorticoid administration in all three patients.Fig. 1

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