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Neely, Michael; Rushing, Teresa; Kovacs, Andrea; Jelliffe, Roger; Hoffman, Jill
Clinical infectious diseases, 01/2010, Letnik: 50, Številka: 1Journal Article
Background Voriconazole pharmacokinetic and pharmacodynamic data are lacking in children. Methods Records at the Childrens Hospital Los Angeles were reviewed for children with ⩾ 1 serum voriconazole concentration measured from 1 May 2006 through 1 June 2007. Information on demographic characteristics, dosing histories, serum concentrations, toxicity and survival, and outcomes was obtained. Results A total of 207 voriconazole measurements were obtained from 46 patients (age, 0.8–20.5 years). A 2-compartment Michaelis-Menten pharmacokinetic model fit the data best but explained only 80% of the observed variability. The crude mortality rate was 28%, and each trough serum voriconazole concentration < 1000 ng/mL was associated with a 2.6-fold increased odds of death (95% confidence interval, 1.6–4.8; P p.002). Serum voriconazole concentrations were not associated with hepatotoxicity. Simulations predicted an intravenous dose of 7 mg/kg or an oral dose of 200 mg twice daily would achieve a trough >1000 ng/mL in most patients, but with a wide range of possible concentrations. Conclusions We found a pharmacodynamic association between a voriconazole trough >1000 ng/mL and survival and marked pharmacokinetic variability, particularly after enteral dosing, justifying the measurement of serum concentrations.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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in: SICRIS
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