HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Pharmacologic considerations for oseltamivir disposition: focus on the neonate and young infant.

Abstract
Across much of the world, pandemic H1N1 infection has produced a significant healthcare crisis, reflected in significant morbidity and mortality. Statistics reveal that infection-associated deaths among individuals without pre-existing conditions (e.g. immunosuppression) are clustered in pregnant women and young infants. In developing countries where the availability of influenzae vaccine is limited, the only currently available pharmacologic counter-measure for H1N1 disease is oseltamivir, a neuraminidase inhibitor with excellent in vitro activity against the virus. This drug is available in oral solid and liquid formulations, has excellent peroral bioavailability in adults, and generally has a very favorable safety profile. Many observational studies indicate that oseltamivir treatment is associated with symptomatic improvement in pediatric patients with H1N1 infection and, therefore, is considered to represent a viable therapeutic option for use in children. However, the disposition of the ethyl ester prodrug and its active metabolite has not been well characterized in infants and children. Presently, data are available from only two published investigations and preliminary summary information from a recent presentation of an ongoing study. Given that recent in vitro data support the importance of a target exposure-response profile for the active metabolite of oseltamivir and that many processes known to modulate drug disposition have a developmental basis, understanding the potential impact of age on oseltamivir disposition becomes crucial in the development of age-appropriate dosing regimens for the drug. In this review, the impact of ontogeny on processes that are important in regulating the absorption, distribution, metabolism, and excretion of oseltamivir and its active metabolite are considered. Data from both animal and human investigations are presented in the context of defining how development might influence the dose-exposure relationship and, most importantly, the significant variability associated with it. In addition, the available pediatric pharmacokinetic data for oseltamivir and its active metabolite are summarized and current 'information gaps' deserving of future study are presented.
AuthorsSusan M Abdel-Rahman, Jason G Newland, Gregory L Kearns
JournalPaediatric drugs (Paediatr Drugs) Vol. 13 Issue 1 Pg. 19-31 (Feb 01 2011) ISSN: 1179-2019 [Electronic] Switzerland
PMID21162598 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Antiviral Agents
  • Prodrugs
  • Oseltamivir
Topics
  • Adult
  • Age Factors
  • Animals
  • Antiviral Agents (administration & dosage, pharmacokinetics, therapeutic use)
  • Biological Availability
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Influenza A Virus, H1N1 Subtype (drug effects)
  • Influenza, Human (drug therapy, virology)
  • Oseltamivir (administration & dosage, pharmacokinetics, therapeutic use)
  • Pregnancy
  • Prodrugs

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: