Pharmacokinetics of drugs in neonates: pattern recognition beyond compound specific observations

Current Pharmaceutical Design
Anne SmitsKarel Allegaert

Abstract

Although the principles of drug disposition also apply in neonates, their specific characteristics warrant focussed assessment. Children display maturation in drug disposition, but this is most prominent in the first year of life. Besides maturational aspects of drug absorption and distribution, maturation mainly relates to (renal) elimination and (hepatic) metabolic clearance. Renal elimination clearance in early life is low and almost completely depends on glomerular filtration. Despite the overall low clearance, interindividual variability is already extensive and can be predicted by covariates like postmenstrual age, postnatal age, co-administration of a non-selective cyclo-oxygenase inhibitor, growth restriction or peripartal asphyxia. These findings are illustrated by observations on amikacin and vancomycin. Variation in phenotypic metabolic clearance is based on constitutional, environmental and genetic characteristics. In early life, it mainly reflects ontogeny, but other covariates may also become relevant. Almost all phase I and phase II metabolic processes display ontogeny in a iso-enzyme specific pattern. The impact of covariates like postmenstrual age, postnatal age, disease state characteristics and polymorphisms ...Continue Reading

Citations

Jan 8, 2013·European Journal of Pediatrics·Karel Allegaert
Sep 11, 2014·The Journal of Maternal-fetal & Neonatal Medicine : the Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians·Daniela FanniGavino Faa
May 12, 2015·Expert Opinion on Drug Metabolism & Toxicology·Janko SamardzicKarel Allegaert
Jun 26, 2014·Expert Opinion on Drug Metabolism & Toxicology·Karel Allegaert
Apr 27, 2013·Paediatric Anaesthesia·Karel AllegaertJohn van den Anker
Oct 5, 2013·Journal of Chemotherapy·Gian Maria Pacifici, Karel Allegaert
Jan 24, 2016·Archives of Disease in Childhood·Steven Pauwels, Karel Allegaert
Jun 23, 2015·Clinical Pharmacology and Therapeutics·K Allegaert, J van den Anker
May 5, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Raffaele CoppiniKarel Allegaert
Oct 11, 2014·Expert Review of Anti-infective Therapy·Chris StockmannCatherine M T Sherwin
Jan 31, 2018·Antimicrobial Agents and Chemotherapy·Yuma A BijleveldUNKNOWN PharmaCool Study Group
Feb 8, 2013·World Journal of Clinical Pediatrics·Karel Allegaert
Oct 10, 2018·Therapeutic Drug Monitoring·Xiaoxi LiuCatherine M T Sherwin
Jan 1, 2021·Journal of Clinical Pharmacology·Brooks T McPhailAlexander A Vinks
Jul 10, 2019·Journal of Clinical Pharmacology·Hechuan WangVijay Ivaturi

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