tetano
Editor, Senior Moderator
Antimicrob Agents Chemother. 2012 May 7. [Epub ahead of print]
Oseltamivir Pharmacokinetics and Clinical Experience in Neonates and Infants during an Outbreak of Influenza A (H1N1) on a Neonatal Intensive Care Unit.
Standing JF, Nika A, Tsagris V, Kapetanakis I, Maltezou HC, Kafetzis DA, Tsolia MN.
Source
Infectious Diseases and Microbiology Unit, University College London, Institute of Child Health, London, WC1N 1EH, UK.
Abstract
Background: Detailed oseltamivir pharmacokinetics have yet to be reported in neonates and infants; this group is at high risk of serious influenza-associated complications. Extrapolation of doses from older patients is complicated by rapid organ and drug-metabolizing enzyme maturation. A pharmacokinetic study has been conducted during an influenza A (H1N1) outbreak in a neonatal intensive care unit.Methods: Each included patient provided 4 samples for oseltamivir and 4 samples for its active metabolite oseltamivir carboxylate. A population pharmacokinetic model was developed with NONMEM. Allometric weight scaling and maturation functions were added a priori to scale for size and age based on literature values.Results: Nine neonates and infants were recruited. A physiologically parameterised pharmacokinetic model predicted typical Day 1 area under the curve (AUC((0-12))) values of 1966 and 2484 μg.h/L for neonates and infants ≤ 37 weeks postmenstrual age (PMA) and >37 weeks PMA treated with 1 mg/kg and 2 mg/kg respectively. Corresponding steady state AUC((0-12)) values were 3670 and 4559 μg.h/L.Conclusion: Premature neonates treated with 1 mg/kg and term babies with 2 mg/kg should have expected average oseltamivir carboxylate concentrations of similar range to adults treated with 75 mg, and this corresponds to over 200-fold above the half maximal inhibitory concentration (IC(50)) value for influenza A (H1N1) from the start of therapy.
PMID:
22564835
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22564835
Oseltamivir Pharmacokinetics and Clinical Experience in Neonates and Infants during an Outbreak of Influenza A (H1N1) on a Neonatal Intensive Care Unit.
Standing JF, Nika A, Tsagris V, Kapetanakis I, Maltezou HC, Kafetzis DA, Tsolia MN.
Source
Infectious Diseases and Microbiology Unit, University College London, Institute of Child Health, London, WC1N 1EH, UK.
Abstract
Background: Detailed oseltamivir pharmacokinetics have yet to be reported in neonates and infants; this group is at high risk of serious influenza-associated complications. Extrapolation of doses from older patients is complicated by rapid organ and drug-metabolizing enzyme maturation. A pharmacokinetic study has been conducted during an influenza A (H1N1) outbreak in a neonatal intensive care unit.Methods: Each included patient provided 4 samples for oseltamivir and 4 samples for its active metabolite oseltamivir carboxylate. A population pharmacokinetic model was developed with NONMEM. Allometric weight scaling and maturation functions were added a priori to scale for size and age based on literature values.Results: Nine neonates and infants were recruited. A physiologically parameterised pharmacokinetic model predicted typical Day 1 area under the curve (AUC((0-12))) values of 1966 and 2484 μg.h/L for neonates and infants ≤ 37 weeks postmenstrual age (PMA) and >37 weeks PMA treated with 1 mg/kg and 2 mg/kg respectively. Corresponding steady state AUC((0-12)) values were 3670 and 4559 μg.h/L.Conclusion: Premature neonates treated with 1 mg/kg and term babies with 2 mg/kg should have expected average oseltamivir carboxylate concentrations of similar range to adults treated with 75 mg, and this corresponds to over 200-fold above the half maximal inhibitory concentration (IC(50)) value for influenza A (H1N1) from the start of therapy.
PMID:
22564835
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22564835