is minimal information regarding the development of CYP2C19 metabolism.Given that voriconazole clearance is dependent on CYP2C19 and to a lesser extent CYP2C9 and CYP3A4, there is potential for drug-drug interactions. The manufacturer has recommended that, if voriconazole is given with phenytoin in adults, the voriconazole dosage should be increased from 4 mg/kg to 5 mg/kg every 12 h. In addition the manufacturer considers the concomitant use of long-acting barbiturates with voriconazole to be contraindicated because of lack of data. Long-acting barbiturates, such as phenobarbital, are inducers of CYP450 enzymes.The third and fourth sets of voriconazole concentrations were collected while the patient was receiving phenobarbital and demonstrated the impact of phenobarbital on the metabolism of voriconazole. The third set of concentrations was reduced to a greater degree than expected based on the patient's weight gain. Even a dosage increase of ϳ25% did not result in a detectable trough concentration.In conclusion we effectively treated a neutropenic infant with voriconazole for a skin infection that grew T. beigelii. No adverse effects were specifically associated with voriconazole. However, the serum drug concentrations for the given doses in this infant were lower than would have been expected based on the pharmacokinetic data in adults. This leads to the conclusion that both volume of distribution and clearance are increased compared with adults (i.e. decreased peak and undetectable trough). The addition of chronic phenobarbital therapy further reduced voriconazole concentrations. In this infant, if the clinical condition (i.e. invasive fungal infection or poor clinical response) had warranted a more aggressive dosage, an increased milligram/kg/dose and dosing frequency would have been recommended (e.g. 8 mg/kg/dose every 8 h).
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