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Development of a Generic Fetal Physiologically Based Pharmacokinetic Model and Prediction of Human Maternal and Fetal Organ Concentrations of Cefuroxime.
Liu, Xiaomei I; Green, Dionna J; van den Anker, John; Ahmadzia, Homa K; Burckart, Gilbert J; Dallmann, André.
Afiliación
  • Liu XI; Division of Clinical Pharmacology, Children's National Hospital, Washington, DC, USA. rph5862@gmail.com.
  • Green DJ; Office of Pediatric Therapeutics, US Food and Drug Administration, Silver Spring, MD, USA.
  • van den Anker J; Division of Clinical Pharmacology, Children's National Hospital, Washington, DC, USA.
  • Ahmadzia HK; Division of Maternal-Fetal Medicine, Department of OB/Gyn, George Washington University, Washington, DC, USA.
  • Burckart GJ; Office of Clinical Pharmacology, US Food and Drug Administration, Silver Spring, MD, USA.
  • Dallmann A; Bayer HealthCare SAS, Loos, France.
Clin Pharmacokinet ; 63(1): 69-78, 2024 01.
Article en En | MEDLINE | ID: mdl-37962827
BACKGROUND AND OBJECTIVE: Physiologically based pharmacokinetic (PBPK) models for pregnant women have recently been successfully used to predict maternal and umbilical cord pharmacokinetics (PK). Because there is very limited opportunity for conducting clinical and PK investigations for fetal drug exposure, PBPK models may provide further insights. The objectives of this study were to extend a whole-body pregnancy PBPK model by multiple compartments representing fetal organs, and to predict the PK of cefuroxime in the maternal and fetal plasma, the amniotic fluid, and several fetal organs. METHODS: To this end, a previously developed pregnancy PBPK model for cefuroxime was updated using the open-source software Open Systems Pharmacology (PK-Sim®/MoBi®). Multiple compartments were implemented to represent fetal organs including brain, heart, liver, lungs, kidneys, the gastrointestinal tract (GI), muscles, and fat tissue, as well as another compartment lumping organs and tissues not explicitly represented. RESULTS: This novel PBPK model successfully predicted cefuroxime concentrations in maternal blood, umbilical cord, amniotic fluid, and several fetal organs including heart, liver, and lungs. Further model validation with additional clinical PK data is needed to build confidence in the model. CONCLUSIONS: Being developed with an open-source software, the presented generic model can be freely re-used and tailored to address specific questions at hand, e.g., to assist the design of clinical studies in the context of drug research or to predict fetal organ concentrations of chemicals in the context of fetal health risk assessment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cefuroxima / Modelos Biológicos Límite: Female / Humans / Pregnancy Idioma: En Revista: Clin Pharmacokinet Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cefuroxima / Modelos Biológicos Límite: Female / Humans / Pregnancy Idioma: En Revista: Clin Pharmacokinet Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza