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In this population, dose selection to achieve safe and effective drug exposure is difficult. We developed a novel and flexible approach that uses physiologically based pharmacokinetic (<jats:styled-content style=\"fixed-case\">PBPK<\/jats:styled-content>) modeling to translate results from<jats:styled-content style=\"fixed-case\">ECMO<\/jats:styled-content><jats:italic>ex vivo<\/jats:italic>experiments into bedside dosing recommendations. To determine fluconazole dosing in children on<jats:styled-content style=\"fixed-case\">ECMO<\/jats:styled-content>, we developed a<jats:styled-content style=\"fixed-case\">PBPK<\/jats:styled-content>model, which was validated using fluconazole pharmacokinetic (<jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>) data in adults and critically ill infants. 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