Challenges for drug studies in children: CYP3A phenotyping as example

Drug Discovery Today
S N de WildtGideon Koren

Abstract

A paucity of data exists on the disposition and effect of drugs in young children. This information gap can be reduced by elucidating developmental principles of absorption, distribution, metabolism and excretion (ADME) in vivo. Such knowledge might enable the prediction of the disposition of individual drugs in children over the whole pediatric age range. CYP3A, the most abundant human drug metabolizing enzyme, is involved in the metabolism of more than 50% of all marketed drugs. Hence, elucidating the developmental pattern of CYP3A in relation to genetic background, disease and comedications might greatly enhance our knowledge on drug disposition in children. Several methods have been used to determine in vivo CYP3A activity in human adults, while similar studies in children face several ethical, practical and scientific challenges. The aim of this review is to identify these challenges and offer feasible solutions for studying drugs in young children, with an emphasis on CYP3A phenotyping as an example.

References

Jan 1, 1992·European Journal of Clinical Pharmacology·E Jacqz-AigrainF Beaufils
Jan 1, 1992·Critical Reviews in Toxicology·S A Wrighton, J C Stevens
Jan 1, 1985·European Journal of Clinical Pharmacology·L D BornemannI H Patel
Apr 1, 1985·Mayo Clinic Proceedings·J A Washington, W R Wilson
Mar 1, 1985·Mayo Clinic Proceedings·J A Washington, W R Wilson
May 1, 1981·Antimicrobial Agents and Chemotherapy·P PatamasuconJ D Nelson
Mar 1, 1981·British Journal of Anaesthesia·J B Eisenkraft, R Miller
Aug 1, 1994·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Y CakalogluR Williams
Aug 1, 1994·Pharmacogenetics·P B Watkins
Jan 1, 1993·Fundamental & Clinical Pharmacology·G PonsE Bellissant
Jun 1, 1996·Therapeutic Drug Monitoring·A H ThomsonS Wright
Jan 1, 1996·European Journal of Clinical Pharmacology·F Vauzelle-KervroedanG Pons
Jan 16, 1999·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·G T TuckerP R Jackson
Jan 11, 2000·Clinical Pharmacokinetics·S N de WildtJ N van den Anker
Oct 14, 2000·The New England Journal of Medicine·G W 't JongJ N van den Anker
Jul 4, 2001·Pharmacogenetics·D S StreetmanA N Nafziger
Apr 23, 2002·British Journal of Clinical Pharmacology·S N de WildtJ N van den Anker
Jul 19, 2002·Drug Metabolism and Disposition : the Biological Fate of Chemicals·J Andrew WilliamsSteven A Wrighton
Apr 17, 2003·Intensive Care Medicine·Joseph A CarcilloGilbert J Burckart
May 29, 2003·Critical Care Medicine·Curtis E HaasWilliam Reiss
Jul 9, 2003·Critical Care Medicine·S N de WildtJ N van den Anker
Aug 12, 2003·American Journal of Physiology. Gastrointestinal and Liver Physiology·W P D LemahieuY Vanrenterghem
Sep 17, 2003·The Journal of Pharmacology and Experimental Therapeutics·Jeffrey C StevensMatthew J Zaya
Sep 19, 2003·The New England Journal of Medicine·Gregory L KearnsRalph E Kauffman
Nov 8, 2003·Pediatric Research·Sophie R D van der SchoorJohannes B van Goudoever
May 6, 2004·International Journal of Clinical Pharmacology and Therapeutics·I Mahmood, V Tammara
Sep 24, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Weili HuangKenneth E Thummel
Nov 17, 2004·Journal of Clinical Pharmacology·Mahmut OzdemirAmin Rostami-Hodjegan
Dec 30, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Sharyn D BakerAlex Sparreboom
Feb 9, 2005·British Journal of Pharmacology·Josée MichaudVincent Pichette
Apr 23, 2005·The Journal of Pharmacology and Experimental Therapeutics·J Steven LeederRobin E Pearce
May 6, 2005·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Katarina AleksaGideon Koren
Jul 29, 2005·Drug Metabolism and Disposition : the Biological Fate of Chemicals·May FakhouryEvelyne Jacqz-Aigrain
Oct 26, 2005·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Carrie A VyhlidalJ Steven Leeder

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Citations

Nov 23, 2011·Biomarkers in Medicine·Jennifer GoldmanJ Steven Leeder
Nov 1, 2009·Future Medicinal Chemistry·James H Doroshow, Shivaani Kummar
Jun 13, 2012·Expert Opinion on Drug Metabolism & Toxicology·Miriam G MooijSaskia N de Wildt
May 10, 2011·Expert Opinion on Drug Metabolism & Toxicology·Saskia N de Wildt
Nov 23, 2010·British Journal of Clinical Pharmacology·Massimo CellaOscar Della Pasqua
Mar 8, 2016·Expert Opinion on Drug Metabolism & Toxicology·Nicolas HohmannGerd Mikus
Dec 12, 2013·British Journal of Clinical Pharmacology·Pathma D JosephDr Patrina Hy Caldwell
Feb 27, 2016·Clinical and Translational Science·T BurtM Rowland
Feb 6, 2017·Clinical Pharmacokinetics·Miriam G MooijSaskia N de Wildt
Jun 22, 2010·European Journal of Epidemiology·François AngoulvantCorinne Alberti
Jul 4, 2019·British Journal of Clinical Pharmacology·Bianca D van GroenMark A Turner
Jul 3, 2013·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Robin E PearceGregory L Kearns
May 14, 2020·Clinical Pharmacology and Therapeutics·Bianca D van GroenSaskia N de Wildt
Jan 1, 2021·Journal of Clinical Pharmacology·Brooks T McPhailAlexander A Vinks

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