Factors and Mechanisms for Pharmacokinetic Differences between Pediatric Population and Adults.docVIP

Pharmaceutics 2011, 3, 53-72; doi: 10.3390/pharmaceutics3010053 OPEN ACCESS pharmaceutics ISSN 1999-4923 /journal/pharmaceutics Review Factors and Mechanisms for Pharmacokinetic Differences between Pediatric Population and Adults Eva Fernandez 1,*, Raul Perez 1 , Alfredo Hernandez 1, Pilar Tejada 1, Marta Arteta 1 and Jose T. Ramos 2,* 1 Department of Pharmacy, Getafe University Hospital, Carretera Toledo Km 12,5 Getafe, Madrid, Spain 2 Department of Paediatrics, Getafe University Hospital, Carretera Toledo Km 12,5 Getafe, Madrid, Spain * Author to whom correspondence should be addressed; E-Mails: efernandeze.hugf@ (E.F.); jtramos.hugf@ (J.T.R.); Tel.: +34-916-247-265; Fax: +34-916-247-308. Received: 16 December 2010 / Accepted: 28 January 2011 / Published: 7 February 2011 Abstract: Many physiologic differences between children and adults may result in age-related changes in pharmacokinetics and pharmacodynamics. Factors such as gastric pH and emptying time, intestinal transit time, immaturity of secretion and activity of bile and pancreatic fluid among other factors determine the oral bioavailability of pediatric and adult populations. Anatomical, physiological and biochemical characteristics in children also affect the bioavailability of other routes of administration. Key factors explaining differences in drug distribution between the pediatric population and adults are membrane permeability, plasma protein binding and total body water. As far as drug metabolism is concerned, important differences have been found in the pediatric population compared with adults both for phase I and phase II metabolic enzymes. Immaturity of glomerular filtration, renal tubular secretion and tubular reabsorption at birth and their maturation determine the different excretion of drugs in the pediatric population compared to adults. Keywords: pharmacokinetics; children; neonates; infants;