title: ABCB1 polymorphisms and neuropsychiatric adverse events in oseltamivir-treated children during influenza H1N1/09 pandemia.
abstract: OBJECTIVE
  To examine the safety profile of oseltamivir in children and evaluate the impact of P-glycoprotein polymorphisms on the incidence of neuropsychiatric adverse events (NPAE) in oseltamivir-treated children.
  
  
  METHODS
  This prospective cohort study was conducted in our tertiary care pediatric hospital (University Hospitals of Geneva, Switzerland) during the H1N1 pandemia, between 1 October 2009 and 31 January 2010. All newborn to 18 year-old patients presenting at the emergency department with a flu-like illness were eligible for inclusion. Adverse events were systematically recorded by pediatricians and/or by parents at home using a diary card, with a 30-day follow-up period. The causality assessment of oseltamivir in NPAE was performed by two clinical pharmacologists. After informed consent, enrolled patients were also genotyped for ABCB1 3435C>T (rs1045642) and 2677G>T/A (rs2032582) polymorphisms.
  
  
  RESULTS
  Among the 42 H1N1-infected, oseltamivir-treated children who were genotyped for ABCB1 3435C>T and 2677G>T/A variants, 36% presented NPAE. When examining the association between the diplotype and the development of NPAE, we observed that the frequency of NPAE displayed a 'genotype-trend effect' with the variant and the wild-type subgroups at the two far ends. A total of 11% of the 2677GG-3435CC individuals (wild-type homozygous) presented NPAE, compared with 39% of the individuals being heterozygous for at least one variant allele and 67% of the 2677TT-3435TT individuals (homozygous variants) (p = 0.149, nonsignificant).
  
  
  CONCLUSIONS
  These observations suggest a potential influence of ABCB1 polymorphisms in oseltamivir-related NPAE, maybe as a result of an enhanced permeability of the blood-brain barrier to oseltamivir
authors: Geneva Medical Faculty & University Hospitals of Geneva, Department of Pediatrics, Geneva, Switzerland.
authors: Arnaud G
authors: AG
authors: L'Huillier
authors: Kuntheavy
authors: K
authors: Ing Lorenzini
authors: Pierre-Alex
authors: PA
authors: Crisinel
authors: Michela C
authors: MC
authors: Rebsamen
authors: Joel
authors: J
authors: Fluss
authors: Christian M
authors: CM
authors: Korff
authors: Remy P
authors: RP
authors: Barbe
authors: Claire-Anne
authors: CA
authors: Siegrist
authors: Pierre
authors: P
authors: Dayer
authors: Klara M
authors: KM
authors: Posfay-Barbe
authors: Jules A
authors: JA
authors: Desmeules
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000293:Adolescent; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002199:Capillary Permeability / Q000187:drug effects / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053118:Influenza A Virus, H1N1 Subtype; D007251:Influenza, Human / Q000188:drug therapy*; D001523:Mental Disorders / Q000139:chemically induced* / Q000235:genetics; D053139:Oseltamivir / Q000009:adverse effects* / Q000627:therapeutic use; D058873:Pandemics; D020641:Polymorphism, Single Nucleotide
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000998:Antiviral Agents; D053139:Oseltamivir