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- W2323950043 abstract "Introduction: Voriconazole (VOR) and posaconazole (POS) are associated with large inter-subject pharmacokinetic variability; however, the role of therapeutic drug monitoring (TDM) has yet to be clearly defined for these agents. The purpose of this study was to evaluate the utility of TDM for identifying subtherapeutic VOR and POS levels. Hypothesis: A significant proportion of VOR and POS levels will be subtherapeutic, signaling the need for a dosage adjustment. Methods: A retrospective evaluation of all VOR and POS serum levels obtained in adult patients at our center was performed. Goal levels for treatment and prophylaxis were >1.0 and >0.5 mcg/mL for VOR and >0.7 and >0.2 mcg/mL for POS, respectively. The primary outcome was the proportion of subtherapeutic VOR and POS levels. The proportion of subtherapeutic VOR and POS levels in critically ill (ICU) versus non-ICU patients was also compared. Results: Ninety-nine trough levels (85 VOR and 14 POS) were evaluated in 54 patients. The mean total daily dose (TDD) of VOR and POS were 628 mg and 943 mg, achieving mean ± SD concentrations of 2.71 ± 2.4 mcg/ml and 0.81 ± 1.8 mcg/mL, respectively. Overall, 37% of VOR and POS levels were subtherapeutic; levels of POS were subtherapeutic more frequently than VOR [10 of 14 (71%) vs. 27 of 85 (32%), p=0.007]. Levels were more often obtained from patients receiving VOR intravenously (IV) in ICU versus non-ICU patients [18 of 29 (62%) vs. 23 of 56 (41%), p=0.07], and despite a lower TDD, were less likely to be subtherapeutic [5 of 29 (17%) vs. 22 of 56 (39%), p=0.05, (TDD = 558 ± 188 vs. 644 ± 234 mg, p=0.04)]. There was no significant difference between the ICU and non-ICU groups for POS. Conclusions: A substantial proportion of VOR and POS levels were subtherapeutic, suggesting that TDM may be a useful tool for optimizing drug exposure. The use of IV VOR or decreased drug clearance due to a higher prevalence and/or severity of organ dysfunction in ICU patients compared to non-ICU patients may account for the smaller proportion of subtherapeutic VOR levels. Bioavailability of oral VOR and POS may also be reduced compared to healthy subjects." @default.
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- W2323950043 date "2012-12-01" @default.
- W2323950043 modified "2023-09-27" @default.
- W2323950043 title "921" @default.
- W2323950043 doi "https://doi.org/10.1097/01.ccm.0000425136.97273.11" @default.
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