ABCB1 polymorphisms and neuropsychiatric adverse events in oseltamivir-treated children during influenza H1N1/09 pandemia
| Autor: | Arnaud G, L'Huillier, Kuntheavy, Ing Lorenzini, Pierre-Alex, Crisinel, Michela C, Rebsamen, Joel, Fluss, Christian M, Korff, Remy P, Barbe, Claire-Anne, Siegrist, Pierre, Dayer, Klara M, Posfay-Barbe, Jules A, Desmeules, Barbara, Wildhaber |
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| Přispěvatelé: | Korff, Christian, Barazzone, Constance, Beghetti, Maurice, Belli, Dominique Charles, Berner, Michel, Delco, Cristina Maria, Galetto-Lacour, Annick, Gervaix, Alain, Girardin, Eric, Mclin, Valérie Anne, Ozsahin, Ayse Hulya, Taguebue, Jean, Tempia-Caliera Schaeppi, Michela, Wagner, Noémie, Wildhaber, Barbara |
| Rok vydání: | 2011 |
| Předmět: |
Pediatrics
Influenza Human/drug therapy viruses Influenza h1n1 ddc:616.07 chemistry.chemical_compound ddc:616.89 Influenza A Virus H1N1 Subtype Informed consent Capillary Permeability/drug effects/genetics Medicine Prospective cohort study Child ddc:616 ddc:615 ddc:618 ddc:617 Oseltamivir/adverse effects/therapeutic use Incidence (epidemiology) Mental Disorders virus diseases Blood-Brain Barrier Child Preschool Antiviral Agents/adverse effects/therapeutic use Molecular Medicine Blood-Brain Barrier/drug effects Oseltamivir medicine.medical_specialty ATP Binding Cassette Transporter Subfamily B Adolescent Antiviral Agents Polymorphism Single Nucleotide P-Glycoprotein/genetics Capillary Permeability ddc:610/370 Influenza Human Genetics Humans ATP Binding Cassette Transporter Subfamily B Member 1 Adverse effect Pandemics Pharmacology business.industry Infant Newborn Infant Emergency department Mental Disorders/chemically induced/genetics biochemical phenomena metabolism and nutrition respiratory tract diseases chemistry business Pharmacogenetics |
| Zdroj: | Pharmacogenomics, Vol. 12, No 10 (2011) pp. 1493-501 |
| ISSN: | 1744-8042 1462-2416 |
| Popis: | Aims: 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. Subjects & 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). Conclusion: 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. Original submitted 26 April 2011; revision submitted 30th June 2011 |
| Databáze: | OpenAIRE |
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