Pediatric Dosing and Body Size in Biotherapeutics 英文参考文献.docVIP

Pharmaceutics 2010, 2, 389-418; doi:10.3390/pharmaceutics2040389 OPEN ACCESS pharmaceutics ISSN 1999-4923 /journal/pharmaceutics Review Pediatric Dosing and Body Size in Biotherapeutics Rong Shi and Hartmut Derendorf * Department of Pharmaceutics, University of Florida, Gainesville, FL, 32610, USA; E-Mail: rongshi@. * Author to whom correspondence should be addressed; E-Mail: hartmut@; Tel.: +1- 352-273-7856; Fax: +1- 352-392-3249. Received: 26 October 2010; in revised form: 9 December 2010 / Accepted: 15 December 2010/ Published: 16 December 2010 Abstract: Although pediatric doses for biotherapeutics are often based on patients body weight (mg/kg) or body surface area (mg/m2), linear body size dose adjustment is highly empirical. Growth and maturity are also important factors that affect the absorption, distribution, metabolism and excretion (ADME) of biologics in pediatrics. The complexity of the factors involved in pediatric pharmacokinetics lends to the reconsideration of body size based dose adjustment. A proper dosing adjustment for pediatrics should also provide less intersubject variability in the pharmacokinetics and/or pharmacodynamics of the product compared with no dose adjustment. Biological proteins and peptides generally share the same pharmacokinetic principle with small molecules, but the underlying mechanism can be very different. Here, pediatric and adult pharmacokinetic parameters are compared and summarized for selected biotherapeutics. The effect of body size on the pediatric pharmacokinetics for these biological products is discussed in the current review. Keywords: pediatric; dosing; proteins; peptides 1. Introduction Due to the complexity and costs of pediatric safety and efficacy studies, pharmaceutical companies are somewhat reluctant to study drugs and biological products in children. Without safety and efficacy studies in children, physicians ar