Review ArticleReview Article
Open Access
Ontogeny of Hepatic Transporters and Drug-Metabolizing Enzymes in Humans and in Nonclinical Species
B. D. van Groen, J. Nicolaï, A. C. Kuik, S. Van Cruchten, E. van Peer, A. Smits, S. Schmidt, S. N. de Wildt, K. Allegaert, L. De Schaepdrijver, P. Annaert and J. Badée
Hyunyoung Jeong, ASSOCIATE EDITOR
Pharmacological Reviews April 2021, 73 (2) 597-678; DOI: https://doi.org/10.1124/pharmrev.120.000071
B. D. van Groen
Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands (B.D.v.G., K.A.); Development Science, UCB BioPharma SRL, Braine-l’Alleud, Belgium (J.N.); Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands (A.C.K.); Department of Veterinary Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Wilrijk, Belgium (S.V.C.); Fendigo sa/nvbv, An Alivira Group Company, Brussels, Belgium (E.v.P.); Department of Development and Regeneration KU Leuven, Leuven, Belgium (A.S.); Neonatal intensive care unit, University Hospitals Leuven, Leuven, Belgium (A.S.); Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, Florida (S.S.); Department of Pharmacology and Toxicology, Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands (S.N.d.W.); Departments of Development and Regeneration and of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium (K.A.); Department of Hospital Pharmacy, Erasmus MC, University Medical Center, Rotterdam, The Netherlands (K.A.); Nonclinical Safety, Janssen R&D, Beerse, Belgium (L.D.S.); Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium (P.A.); and Department of PK Sciences, Novartis Institutes for BioMedical Research, Basel, Switzerland (J.B.)
J. Nicolaï
Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands (B.D.v.G., K.A.); Development Science, UCB BioPharma SRL, Braine-l’Alleud, Belgium (J.N.); Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands (A.C.K.); Department of Veterinary Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Wilrijk, Belgium (S.V.C.); Fendigo sa/nvbv, An Alivira Group Company, Brussels, Belgium (E.v.P.); Department of Development and Regeneration KU Leuven, Leuven, Belgium (A.S.); Neonatal intensive care unit, University Hospitals Leuven, Leuven, Belgium (A.S.); Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, Florida (S.S.); Department of Pharmacology and Toxicology, Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands (S.N.d.W.); Departments of Development and Regeneration and of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium (K.A.); Department of Hospital Pharmacy, Erasmus MC, University Medical Center, Rotterdam, The Netherlands (K.A.); Nonclinical Safety, Janssen R&D, Beerse, Belgium (L.D.S.); Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium (P.A.); and Department of PK Sciences, Novartis Institutes for BioMedical Research, Basel, Switzerland (J.B.)
A. C. Kuik
Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands (B.D.v.G., K.A.); Development Science, UCB BioPharma SRL, Braine-l’Alleud, Belgium (J.N.); Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands (A.C.K.); Department of Veterinary Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Wilrijk, Belgium (S.V.C.); Fendigo sa/nvbv, An Alivira Group Company, Brussels, Belgium (E.v.P.); Department of Development and Regeneration KU Leuven, Leuven, Belgium (A.S.); Neonatal intensive care unit, University Hospitals Leuven, Leuven, Belgium (A.S.); Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, Florida (S.S.); Department of Pharmacology and Toxicology, Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands (S.N.d.W.); Departments of Development and Regeneration and of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium (K.A.); Department of Hospital Pharmacy, Erasmus MC, University Medical Center, Rotterdam, The Netherlands (K.A.); Nonclinical Safety, Janssen R&D, Beerse, Belgium (L.D.S.); Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium (P.A.); and Department of PK Sciences, Novartis Institutes for BioMedical Research, Basel, Switzerland (J.B.)
S. Van Cruchten
Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands (B.D.v.G., K.A.); Development Science, UCB BioPharma SRL, Braine-l’Alleud, Belgium (J.N.); Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands (A.C.K.); Department of Veterinary Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Wilrijk, Belgium (S.V.C.); Fendigo sa/nvbv, An Alivira Group Company, Brussels, Belgium (E.v.P.); Department of Development and Regeneration KU Leuven, Leuven, Belgium (A.S.); Neonatal intensive care unit, University Hospitals Leuven, Leuven, Belgium (A.S.); Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, Florida (S.S.); Department of Pharmacology and Toxicology, Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands (S.N.d.W.); Departments of Development and Regeneration and of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium (K.A.); Department of Hospital Pharmacy, Erasmus MC, University Medical Center, Rotterdam, The Netherlands (K.A.); Nonclinical Safety, Janssen R&D, Beerse, Belgium (L.D.S.); Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium (P.A.); and Department of PK Sciences, Novartis Institutes for BioMedical Research, Basel, Switzerland (J.B.)
E. van Peer
Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands (B.D.v.G., K.A.); Development Science, UCB BioPharma SRL, Braine-l’Alleud, Belgium (J.N.); Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands (A.C.K.); Department of Veterinary Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Wilrijk, Belgium (S.V.C.); Fendigo sa/nvbv, An Alivira Group Company, Brussels, Belgium (E.v.P.); Department of Development and Regeneration KU Leuven, Leuven, Belgium (A.S.); Neonatal intensive care unit, University Hospitals Leuven, Leuven, Belgium (A.S.); Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, Florida (S.S.); Department of Pharmacology and Toxicology, Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands (S.N.d.W.); Departments of Development and Regeneration and of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium (K.A.); Department of Hospital Pharmacy, Erasmus MC, University Medical Center, Rotterdam, The Netherlands (K.A.); Nonclinical Safety, Janssen R&D, Beerse, Belgium (L.D.S.); Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium (P.A.); and Department of PK Sciences, Novartis Institutes for BioMedical Research, Basel, Switzerland (J.B.)
A. Smits
Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands (B.D.v.G., K.A.); Development Science, UCB BioPharma SRL, Braine-l’Alleud, Belgium (J.N.); Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands (A.C.K.); Department of Veterinary Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Wilrijk, Belgium (S.V.C.); Fendigo sa/nvbv, An Alivira Group Company, Brussels, Belgium (E.v.P.); Department of Development and Regeneration KU Leuven, Leuven, Belgium (A.S.); Neonatal intensive care unit, University Hospitals Leuven, Leuven, Belgium (A.S.); Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, Florida (S.S.); Department of Pharmacology and Toxicology, Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands (S.N.d.W.); Departments of Development and Regeneration and of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium (K.A.); Department of Hospital Pharmacy, Erasmus MC, University Medical Center, Rotterdam, The Netherlands (K.A.); Nonclinical Safety, Janssen R&D, Beerse, Belgium (L.D.S.); Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium (P.A.); and Department of PK Sciences, Novartis Institutes for BioMedical Research, Basel, Switzerland (J.B.)
S. Schmidt
Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands (B.D.v.G., K.A.); Development Science, UCB BioPharma SRL, Braine-l’Alleud, Belgium (J.N.); Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands (A.C.K.); Department of Veterinary Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Wilrijk, Belgium (S.V.C.); Fendigo sa/nvbv, An Alivira Group Company, Brussels, Belgium (E.v.P.); Department of Development and Regeneration KU Leuven, Leuven, Belgium (A.S.); Neonatal intensive care unit, University Hospitals Leuven, Leuven, Belgium (A.S.); Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, Florida (S.S.); Department of Pharmacology and Toxicology, Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands (S.N.d.W.); Departments of Development and Regeneration and of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium (K.A.); Department of Hospital Pharmacy, Erasmus MC, University Medical Center, Rotterdam, The Netherlands (K.A.); Nonclinical Safety, Janssen R&D, Beerse, Belgium (L.D.S.); Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium (P.A.); and Department of PK Sciences, Novartis Institutes for BioMedical Research, Basel, Switzerland (J.B.)
S. N. de Wildt
Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands (B.D.v.G., K.A.); Development Science, UCB BioPharma SRL, Braine-l’Alleud, Belgium (J.N.); Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands (A.C.K.); Department of Veterinary Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Wilrijk, Belgium (S.V.C.); Fendigo sa/nvbv, An Alivira Group Company, Brussels, Belgium (E.v.P.); Department of Development and Regeneration KU Leuven, Leuven, Belgium (A.S.); Neonatal intensive care unit, University Hospitals Leuven, Leuven, Belgium (A.S.); Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, Florida (S.S.); Department of Pharmacology and Toxicology, Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands (S.N.d.W.); Departments of Development and Regeneration and of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium (K.A.); Department of Hospital Pharmacy, Erasmus MC, University Medical Center, Rotterdam, The Netherlands (K.A.); Nonclinical Safety, Janssen R&D, Beerse, Belgium (L.D.S.); Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium (P.A.); and Department of PK Sciences, Novartis Institutes for BioMedical Research, Basel, Switzerland (J.B.)
K. Allegaert
Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands (B.D.v.G., K.A.); Development Science, UCB BioPharma SRL, Braine-l’Alleud, Belgium (J.N.); Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands (A.C.K.); Department of Veterinary Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Wilrijk, Belgium (S.V.C.); Fendigo sa/nvbv, An Alivira Group Company, Brussels, Belgium (E.v.P.); Department of Development and Regeneration KU Leuven, Leuven, Belgium (A.S.); Neonatal intensive care unit, University Hospitals Leuven, Leuven, Belgium (A.S.); Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, Florida (S.S.); Department of Pharmacology and Toxicology, Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands (S.N.d.W.); Departments of Development and Regeneration and of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium (K.A.); Department of Hospital Pharmacy, Erasmus MC, University Medical Center, Rotterdam, The Netherlands (K.A.); Nonclinical Safety, Janssen R&D, Beerse, Belgium (L.D.S.); Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium (P.A.); and Department of PK Sciences, Novartis Institutes for BioMedical Research, Basel, Switzerland (J.B.)
L. De Schaepdrijver
Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands (B.D.v.G., K.A.); Development Science, UCB BioPharma SRL, Braine-l’Alleud, Belgium (J.N.); Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands (A.C.K.); Department of Veterinary Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Wilrijk, Belgium (S.V.C.); Fendigo sa/nvbv, An Alivira Group Company, Brussels, Belgium (E.v.P.); Department of Development and Regeneration KU Leuven, Leuven, Belgium (A.S.); Neonatal intensive care unit, University Hospitals Leuven, Leuven, Belgium (A.S.); Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, Florida (S.S.); Department of Pharmacology and Toxicology, Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands (S.N.d.W.); Departments of Development and Regeneration and of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium (K.A.); Department of Hospital Pharmacy, Erasmus MC, University Medical Center, Rotterdam, The Netherlands (K.A.); Nonclinical Safety, Janssen R&D, Beerse, Belgium (L.D.S.); Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium (P.A.); and Department of PK Sciences, Novartis Institutes for BioMedical Research, Basel, Switzerland (J.B.)
P. Annaert
Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands (B.D.v.G., K.A.); Development Science, UCB BioPharma SRL, Braine-l’Alleud, Belgium (J.N.); Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands (A.C.K.); Department of Veterinary Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Wilrijk, Belgium (S.V.C.); Fendigo sa/nvbv, An Alivira Group Company, Brussels, Belgium (E.v.P.); Department of Development and Regeneration KU Leuven, Leuven, Belgium (A.S.); Neonatal intensive care unit, University Hospitals Leuven, Leuven, Belgium (A.S.); Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, Florida (S.S.); Department of Pharmacology and Toxicology, Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands (S.N.d.W.); Departments of Development and Regeneration and of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium (K.A.); Department of Hospital Pharmacy, Erasmus MC, University Medical Center, Rotterdam, The Netherlands (K.A.); Nonclinical Safety, Janssen R&D, Beerse, Belgium (L.D.S.); Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium (P.A.); and Department of PK Sciences, Novartis Institutes for BioMedical Research, Basel, Switzerland (J.B.)
J. Badée
Intensive Care and Department of Pediatric Surgery, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands (B.D.v.G., K.A.); Development Science, UCB BioPharma SRL, Braine-l’Alleud, Belgium (J.N.); Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands (A.C.K.); Department of Veterinary Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Wilrijk, Belgium (S.V.C.); Fendigo sa/nvbv, An Alivira Group Company, Brussels, Belgium (E.v.P.); Department of Development and Regeneration KU Leuven, Leuven, Belgium (A.S.); Neonatal intensive care unit, University Hospitals Leuven, Leuven, Belgium (A.S.); Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, Florida (S.S.); Department of Pharmacology and Toxicology, Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands (S.N.d.W.); Departments of Development and Regeneration and of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium (K.A.); Department of Hospital Pharmacy, Erasmus MC, University Medical Center, Rotterdam, The Netherlands (K.A.); Nonclinical Safety, Janssen R&D, Beerse, Belgium (L.D.S.); Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium (P.A.); and Department of PK Sciences, Novartis Institutes for BioMedical Research, Basel, Switzerland (J.B.)
Hyunyoung Jeong
Roles: ASSOCIATE EDITOR
Data Supplement
- Supplemental Figures -
Supplementary Figures 1 - 21.
- Supplementary Table 1 -
Supplementary Table 1 - Search terms literature search.
- Supplementary Table 2 -
Supplementary Table 2: Gene and protein names of drug transporter isoforms.