tetano
Editor, Senior Moderator
Clin Pharmacol Ther. 2014 May 27. doi: 10.1038/clpt.2014.120. [Epub ahead of print]
The Posology of Oseltamivir in Infants with Influenza Infection Using a Population Pharmacokinetic Approach.
Kamal M1, Acosta E2, Kimberlin D2, Gibiansky L3, Jester P2, Niranjan V4, Rath B5, Clinch B6, S?nchez P7, Ampofo K8, Whitley R2, Rayner C9.
Author information
Abstract
Infants are at increased risk for morbidity and mortality due to influenza. Until recently, few data were available with which to optimize oseltamivir dosing in this high-risk population. Here, data for 133 infants were pooled from two prospective pharmacokinetic/pharmacodynamic safety studies to develop a population pharmacokinetic model. A three-compartment model with allometric scaling of all clearance and volume parameters described the disposition of oseltamivir and its carboxylate metabolite (OC). Weight dependence, OC clearance and volume of distribution increased linearly with age. Analyses showed no association between exposure and viral clearance and the development of resistance (phenotypic/genotypic), normalization of body temperature, or safety endpoints. Pharmacokinetic bridging showed a 3 mg/kg dose yielded acceptable OC exposures and good tolerability while minimizing the risk of underexposure and resistance/treatment failure. These pharmacological analyses formed the basis of the FDA's recent approval of oseltamivir treatment for infants aged as young as 2 weeks with influenza.Clinical Pharmacology & Therapeutics (2014); Accepted article preview online 27 May 2014; doi:10.1038/clpt.2014.120.
PMID:
24865390
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24865390
The Posology of Oseltamivir in Infants with Influenza Infection Using a Population Pharmacokinetic Approach.
Kamal M1, Acosta E2, Kimberlin D2, Gibiansky L3, Jester P2, Niranjan V4, Rath B5, Clinch B6, S?nchez P7, Ampofo K8, Whitley R2, Rayner C9.
Author information
Abstract
Infants are at increased risk for morbidity and mortality due to influenza. Until recently, few data were available with which to optimize oseltamivir dosing in this high-risk population. Here, data for 133 infants were pooled from two prospective pharmacokinetic/pharmacodynamic safety studies to develop a population pharmacokinetic model. A three-compartment model with allometric scaling of all clearance and volume parameters described the disposition of oseltamivir and its carboxylate metabolite (OC). Weight dependence, OC clearance and volume of distribution increased linearly with age. Analyses showed no association between exposure and viral clearance and the development of resistance (phenotypic/genotypic), normalization of body temperature, or safety endpoints. Pharmacokinetic bridging showed a 3 mg/kg dose yielded acceptable OC exposures and good tolerability while minimizing the risk of underexposure and resistance/treatment failure. These pharmacological analyses formed the basis of the FDA's recent approval of oseltamivir treatment for infants aged as young as 2 weeks with influenza.Clinical Pharmacology & Therapeutics (2014); Accepted article preview online 27 May 2014; doi:10.1038/clpt.2014.120.
PMID:
24865390
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24865390