TY - JOUR
TI - Oseltamivir pharmacokinetics and clinical experience in neonates and infants during an outbreak of H1N1 influenza A virus infection in a neonatal intensive care unit
AU - Standing, J.F.
AU - Nika, A.
AU - Tsagris, V.
AU - Kapetanakis, I.
AU - Maltezou, H.C.
AU - Kafetzis, D.A.
AU - Tsolia, M.N.
JO - Antimicrobial Agents and Chemotherapy
PY - 2012
VL - 56
TODO - 7
SP - 3833-3840
PB - 
SN - 0066-4804, 1098-6596
TODO - 10.1128/AAC.00290-12
TODO - 4 acetamido 5 amino 3 (1 ethylpropoxy) 1 cyclohexene 1 carboxylic acid;  oseltamivir, allometry;  area under the curve;  article;  blood sampling;  clinical article;  dehydration;  diarrhea;  distribution volume;  drug absorption;  drug blood level;  drug clearance;  drug disposition;  drug dose increase;  drug transformation;  drug withdrawal;  epidemic;  high risk patient;  human;  IC 50;  infant;  infection prevention;  influenza A (H1N1);  Influenza virus A H1N1;  liver function test;  newborn;  newborn intensive care;  nonhuman;  prematurity;  priority journal;  side effect;  steady state, Antiviral Agents;  Disease Outbreaks;  Female;  Humans;  Infant, Newborn;  Influenza A Virus, H1N1 Subtype;  Influenza, Human;  Intensive Care Units;  Male;  Oseltamivir
TODO - 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. 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. Nine neonates and infants were recruited. A physiologically parameterized pharmacokinetic model predicted typical day 1 area under the curve (AUC 0-12) values of 1,966 and 2,484 μg·h/liter for neonates and infants of ≤37 weeks of postmenstrual age (PMA) and >37 weeks of PMA treated with 1 mg/kg of body weight and 2 mg/kg, respectively. The corresponding steady-state AUC 0-12 values were 3,670 and 4,559 μg·h/liter. Premature neonates treated with 1 mg/kg and term babies treated with 2 mg/kg should have average oseltamivir carboxylate concentrations in a range similar to that for adults treated with 75 mg, corresponding to >200-fold above the half-maximal inhibitory concentration (IC 50) value for influenza A(H1N1) from the start of therapy. Copyright © 2012, American Society for Microbiology. All Rights Reserved.
ER -