For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
40
views
104
references
 Top references
cited by
43
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      359
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Factors and Mechanisms for Pharmacokinetic Differences between Pediatric Population and Adults

      review-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          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.

          Related collections

          Most cited references104

          • Record: found
          • Abstract: not found
          • Article: not found

          Developmental pharmacology--drug disposition, action, and therapy in infants and children.

          Gregory L Kearns, Susan Abdel-Rahman, Sarah Alander … (2003)
          Article 0 comments Cited 183 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Guidelines on paediatric dosing on the basis of developmental physiology and pharmacokinetic considerations.

            Carin M. A. Rademaker, Alfred Schobben, Niek van Wieringen … (2005)
            The approach to paediatric drug dosing needs to be based on the physiological characteristics of the child and the pharmacokinetic parameters of the drug. This review summarises the current knowledge on developmental changes in absorption, distribution, metabolism and excretion and combines this knowledge with in vivo and in vitro pharmacokinetic data that are currently available. In addition, dosage adjustments based on practical problems, such as child-friendly formulations and feeding regimens, disease state, genetic make-up and environmental influences are presented. Modification of a dosage based on absorption, depends on the route of absorption, the physico chemical properties of the drug and the age of the child. For oral drug absorption, a distinction should be made between the very young and children over a few weeks old. In the latter case, it is likely that practical considerations, like appropriate formulations, have much greater relevance to oral drug absorption. The volume of distribution (V(d)) may be altered in children. Hydrophilic drugs with a high V(d) in adults should be normalised to bodyweight in young children (age <2 years), whereas hydrophilic drugs with a low V(d) in adults should be normalised to body surface area (BSA) in these children. For drugs that are metabolised by the liver, the effect of the V(d) becomes apparent in children <2 months of age. In general, only the first dose should be based on the V(d); subsequent doses should be determined by the clearance. Pharmacokinetic studies on renal and liver function clarify that a distinction should be made between maturation and growth of the organs. After the maturation process has finished, the main influences on the clearance of drugs are growth and changes in blood flow of the liver and kidney. Drugs that are primarily metabolised by the liver should be administered with extreme care until the age of 2 months. Modification of dosing should be based on response and on therapeutic drug monitoring. At the age of 2-6 months, a general guideline based on bodyweight may be used. After 6 months of age, BSA is a good marker as a basis for drug dosing. However, even at this age, drugs that are primarily metabolised by cytochrome P450 2D6 and uridine diphosphate glucuronosyltransferase should be normalised to bodyweight. In the first 2 years of life, the renal excretion rate should be determined by markers of renal function, such as serum creatinine and p-aminohippuric acid clearance. A dosage guideline for drugs that are significantly excreted by the kidney should be based on the determination of renal function in first 2 years of life. After maturation, the dose should be normalised to BSA. These guidelines are intended to be used in clinical practice and to form a basis for more research. The integration of these guidelines, and combining them with pharmacodynamic effects, should be considered and could form a basis for further study.
            Article 0 comments Cited 75 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Expression of CYP3A in the human liver--evidence that the shift between CYP3A7 and CYP3A4 occurs immediately after birth.

              T Cresteil, A Moncion, M Sonnier … (1997)
              CYP3A isoforms are responsible for the biotransformation of a wide variety of exogenous chemicals and endogenous steroids in human tissues. Two members of the CYP3A subfamily display developmentally regulated expression in the liver; CYP3A7 is expressed in the fetal liver, whereas CYP3A4 is the major cyrochrome P-450 isoform present in the adult liver. To gain insight into the descriptive ontogenesis of CYP3A isoforms during the neonatal period, we have developed several approaches to explore a neonatal liver bank. Although CYP3A4 and CYP3A7 are structurally closely related, they differ in their capacity to carry out monooxygenase reactions. We have cloned CYP3A4 and CYP3A7 and established stable transfectants in Ad293 cells to investigate their substrate specificities. The 16alpha hydroxylation of dehydroepiandrosterone is catalyzed by both proteins, but CYP3A7 has a higher affinity and maximal velocity than CYP3A4. Conversely, the conversion of testosterone into its 6beta derivative is essentially supported by CYP3A4. We used these two probes to determine the ontogenic evolution at the protein level; CYP3A7 was very active in the fetal liver and its activity was maximal during the first week following birth before to progressively decline and reached a very low level in adult livers. Conversely, the activity of CYP3A4 was extremely weak in the fetus and began to raise after birth to reach 30-40% of the adult activity after one month. CYP3A4 RNA accumulation displays a similar pattern of evolution; when probed with an oligonucleotide, its concentration increased rapidly after birth to reach a plateau as soon as the first week of age. These data supports the assumption that CYP3A4 expression is transcriptionally activated during the first week after birth and is accompanied by a simultaneous decrease of CYP3A7 expression, in such a way that the overall CYP3A protein content and the level of pentoxyresorufin dealkylase catalyzed by the two proteins remain nearly constant.
              Article 0 comments Cited 74 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Pharmaceutics
                Journal ID (iso-abbrev): Pharmaceutics
                Journal ID (publisher-id): Pharmaceutics
                Title: Pharmaceutics
                Publisher: MDPI
                ISSN (Electronic): 1999-4923
                Publication date Collection: March 2011
                Publication date (Electronic): 07 February 2011
                Volume: 3
                Issue: 1
                Pages: 53-72
                Affiliations
                [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 notes
                [* ] Author to whom correspondence should be addressed; E-Mails: efernandeze.hugf@ 123456salud.madrid.org (E.F.); jtramos.hugf@ 123456salud.madrid.org (J.T.R.); Tel.: +34-916-247-265; Fax: +34-916-247-308.
                Article
                Publisher ID: pharmaceutics-03-00053
                DOI: 10.3390/pharmaceutics3010053
                PMC ID: 3857037
                PubMed ID: 24310425
                SO-VID: 577418ba-d664-47e1-a809-d007b90a3393
                Copyright © © 2011 by the authors; licensee MDPI, Basel, Switzerland.
                License:

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                Date received : 16 December 2010
                Date accepted : 28 January 2011
                Categories
                Subject: Review

                Keywords: pharmacokinetics,children,neonates,infants,bioavailability,distribution,metabolism,excretion
                Data availability:
                Keywords: pharmacokinetics, children, neonates, infants, bioavailability, distribution, metabolism, excretion

                Comments

                Comment on this article

                scite_

                Similar content359

                See all similar

                Cited by87

                See all cited by

                Most referenced authors624

                See all reference authors