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Higher exposures are usually required for the treatment of disseminated candidiasis in adults, suggesting that 8?mg/kg may be inadequate in children, especially against organisms with reduced susceptibility. Itraconazole is available in a capsular form, a cyclodextrin-based oral solution, and an intravenous preparation (not widely available in the U.S. or Selleckchem SCH772984 Europe). Doses of 2.5-5.0?mg/kg daily have been used with apparent efficacy [89], [90], [91]?and?[92]; however, there are no PKPD studies available to guide dosing. Limited data suggest the PK of itraconazole are non-linear and highly variable, and that weight-based dosing leads to sub-therapeutic dosing in smaller children [93]?and?[94]. When itraconazole is used, TDM is generally advocated with a target trough levels of >?0.5?mg/L (using HPLC) and 5�C17?mg/L (using bioassay) are extrapolated from studies in adults [95], [96]?and?[97]. Voriconazole is, at present, infrequently used in neonates, its main use being in the treatment of invasive aspergillosis and in fluconazole-resistant candidiasis [98], [99]?and?[100]. Extreme variability in serum concentrations is apparent, with no clear relationship between drug exposure and weight-based dosages [99]. Voriconazole PK in older children and adults is characterised by significant Ritonavir variability in concentration�Ctime profiles and non-linear clearance [101]. Population PK models fitted to paediatric datasets have been used to define regimens for intravenous voriconazole that produce drug exposures comparable with those seen in adults [102]. Population PK analyses have consistently identified considerable PK variability in children, usually making dosing recommendations based on simulation to achieve adult exposures, and providing the basis for TDM [103], [104], [105], [106]?and?[107]. A trough concentration target of 1�C5?mg/L is used in adults receiving voriconazole [108]. In children, trough plasma concentrations www.selleckchem.com/products/dabrafenib-gsk2118436.html that an increase in dose of 1?mg/kg results in an increase in the median trough concentrations by 0.5?mg/L [106]. Posaconazole is only currently available as an oral suspension, and is only licenced for use in children over twelve years. No studies were found that examine posaconazole PK linked with PD in children. Twelve children aged 8�C17?years receiving posaconazole 800?mg daily in divided doses had mean serum concentrations and clinical outcomes comparable with adults [109]. Further studies are required to define appropriate regimens for posaconazole use in children.