Τίτλος:
Oseltamivir pharmacokinetics and clinical experience in neonates and infants during an outbreak of H1N1 influenza A virus infection in a neonatal intensive care unit
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Συγγραφείς:
Standing, J.F.
Nika, A.
Tsagris, V.
Kapetanakis, I.
Maltezou, H.C.
Kafetzis, D.A.
Tsolia, M.N.
Περιοδικό:
Antimicrobial Agents and Chemotherapy
Λέξεις-κλειδιά:
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
DOI:
10.1128/AAC.00290-12
