Considering Age Variation When Coining Drugs as High Versus Low Hepatic Extraction Ratio

The hepatic extraction ratio (EH) is commonly considered an “inherent attribute” of drug. It determines the main physiological and biological elements of the system (patient attributes) that are most significant in interindividual variability of clearance. The EH consists of three age-dependent parameters: fraction of unbound drug in blood (fu.B), hepatic intrinsic clearance of unbound drug […]

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Prediction of Voriconazole Non-linear Pharmacokinetics Using a Pediatric Physiologically-based Pharmacokinetic Modeling Approach

We read with interest the report by Zane and Thakker entitled ‘‘A PBPK model for voriconazole disposition predicts intestinal first-pass metabolism in children’’. We believe the authors should be congratulated for tackling the complex case of voriconazole, as this is a drug with non-linear pharmacokinetics where clinical trials have shown a marked difference between adults […]

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