Document Detail


Antivirals for cytomegalovirus infection in neonates and infants: focus on pharmacokinetics, formulations, dosing, and adverse events.
MedLine Citation:
PMID:  19725597     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cytomegalovirus (CMV) infection is very common throughout the world, and has become more of a pediatric clinical concern given the high incidence of congenital CMV infections as well as the increasing numbers of immunocompromised patients. Because of this, the need for antiviral therapies in infants and neonates is growing. Currently, there are four antivirals available that are active against CMV: ganciclovir, valganciclovir, foscarnet, and cidofovir. At this time, none have approved indications for use in children. Although there are limited data regarding the dose, pharmacokinetics (PK), safety, and adverse events for some of these antivirals, ganciclovir, and its oral prodrug valganciclovir, have been the best studied in the infant and neonate populations. In general, pharmaceutical PK studies in young children are limited by the constraints of sampling difficulties and blood volume requirements; fewer sampling times and studies may be available for drug evaluation. Given this caveat, ganciclovir and valganciclovir PK in children thus far appears to follow a monocompartmental model, contrary to what has been described in adults. However, when normalized for weight, the volume of distribution, clearance, and half-life of ganciclovir are similar to those found in adults. Given the findings that ganciclovir (and thus valganciclovir) clearance is directly proportionate to renal function, care must be taken when administering the drug to patients with impaired renal function. Recent studies evaluating valganciclovir PK in infants (at a dose of 16 mg/kg every 12 hours) have shown similar areas under the plasma concentration-time curve (AUCs) to intravenous ganciclovir (at a dose of 6 mg/kg every 12 hours), and that these AUCs remain quite stable over a number of weeks. As seen in adults, oral ganciclovir has a low bioavailability (4.8% in a pediatric analysis) and is therefore a poor alternative for treating serious CMV infections. Neutropenia is the most frequent toxicity associated with ganciclovir and valganciclovir therapy, whereas significant (and possibly irreversible) renal toxicity can be seen with cidofovir. Foscarnet administration can also result in renal toxicity as well as significant electrolyte imbalances. Several of these drugs have potential toxicities that are of concern, including carcinogenesis, teratogenesis, and azospermia (ganciclovir, valganciclovir, and cidofovir) and deposition into bone or dentition (foscarnet) that may have significant implications when treating an infant. Given these potential ill effects, careful consideration of the indications for the clinical use of these antivirals is necessary before using them for CMV infection in neonates and infants.
Authors:
Beth C Marshall; William C Koch
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Paediatric drugs     Volume:  11     ISSN:  1174-5878     ISO Abbreviation:  Paediatr Drugs     Publication Date:  2009  
Date Detail:
Created Date:  2009-09-03     Completed Date:  2009-11-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100883685     Medline TA:  Paediatr Drugs     Country:  New Zealand    
Other Details:
Languages:  eng     Pagination:  309-21     Citation Subset:  IM    
Affiliation:
Division of Infectious Diseases, Department of Pediatrics, Virginia Commonwealth University Medical Center, Richmond, Virginia, USA. bmarshall@mcvh-vcu.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Antiviral Agents / administration & dosage*,  adverse effects,  pharmacokinetics
Clinical Trials as Topic
Cytomegalovirus Infections / drug therapy*
Dose-Response Relationship, Drug
Humans
Infant
Infant, Newborn
Chemical
Reg. No./Substance:
0/Antiviral Agents

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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