Cytostatic drugs in infants: A review on pharmacokinetic data in infants

van den Berg, Hendrik; van den Anker, John N.; Beijnen, Jos H.

doi:10.1016/j.ctrv.2011.03.005

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Volume 38, Issue 1 , Pages 3-26, February 2012

Cytostatic drugs in infants: A review on pharmacokinetic data in infants

Hendrik van den Berg
- Department of Pediatric Oncology, Emma Children Hospital – Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
- Medicines Evaluation Board, The Hague, The Netherlands
- Corresponding author. Address: Department of Paediatric Oncology, Emma Children Hospital Academic Medical Centre, University of Amsterdam, Room F8-242, P.O. Box 22700, 1100 DD Amsterdam, The Netherlands. Tel.: +31 20 5663050; fax: +31 20 6912231.
John N. van den Anker
- Division of Pediatric Clinical Pharmacology, Children’s National Medical Center, Washington, DC, USA
- Departments of Pediatrics, Pharmacology, and Physiology, George Washington University School of Medicine and Health Sciences, Washington, DC, USA
- Department of Pediatrics, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands
Jos H. Beijnen
- The Netherlands Cancer Institute, Slotervaart Hospital, Amsterdam, The Netherlands

Received 11 January 2011; received in revised form 21 March 2011; accepted 24 March 2011. published online 14 April 2011.

Abstract

Below a certain age protocols in pediatric oncology on cytostatic drug therapy advise use, of other parameters such as weight for dosing; this instead of the most conventional parameter, i.e. body surface area. In infants it is not uncommon that additional reductions are put on top of this for each cytostatic drugs to be administered. The rationale behind this is often lacking. Differences related to the ontogeny of absorption, distribution, metabolism and excretion are often not mentioned. Considering characteristics, such as lipophilia, ionization in relation to pH and size of the molecule and linking these characteristics with age related shifts in the gastrointestinal tract, composition of the body and renal function; predictions on pharmacokinetics (PK) in these infants can to a certain extent be made. More difficult are the shifts in activity of phase I and II enzymes, which are often not known for a specific product. In this review data on the ontogeny of relevant pharmacokinetic pathways in relation to the various cytostatic drugs and data from pharmacokinetic (PK) studies in infants are presented.

This review shows that the administration of cytostatic drugs in infants is often based on limited or even no data at all. Based on such a lack of evidence on treatment of infants with cancer; it should be mandatory that in each infant treated with cytostatic drugs pharmacokinetic data are collected. Compiling these data in a global database would enable evidence-based drug therapy in infants with malignancies, resulting in a more effective treatment with less toxicity in this vulnerable population.

Keywords: Cytostatic drugs, Infant, Pharmacotherapy, Pharmacokinetics, Oncology, Children, Infants, Ontogeny, Metabolism, Allometric scaling