Exploring the roles of UGT1A1 and UGT1A3 in oral clearance of GSK2190915, a 5-lipoxygenase-activating protein inhibitor.
Pharmacogenet Genomics
; 24(12): 618-21, 2014 Dec.
Article
em En
| MEDLINE
| ID: mdl-25192553
ABSTRACT
Pharmacokinetic variability in drug exposure is a concern for all compounds in development including those for the treatment of asthma and other respiratory disorders. Substantial variability in the oral clearance of GSK2190915, a 5-lipoxygenase-activating protein inhibitor that attenuates the production of leukotriene B4 and cysteinyl leukotrienes, is largely unaccounted for by clinical variables. A study of 41 patients, 78% (32/41) of whom were non-Hispanic whites, with mild to moderate asthma identified an association of UGT1A1*28 and UGT1A3*2 with the oral clearance of GSK2190915 (P=3.8×10â»4 and 1.2×10â»5, respectively). However, in a subsequent replication study of 403 non-Hispanic white patients with asthma, we failed to observe a statistically significant association between oral clearance of GSK2190915 and either UGT1A1*28 or UGT1A3*2 (P>0.05). Therefore, genetic effects that could explain the systemic exposure level variability of GSK2190915 were not identified.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ácidos Pentanoicos
/
Asma
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Glucuronosiltransferase
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Indóis
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Humans
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Middle aged
Idioma:
En
Revista:
Pharmacogenet Genomics
Ano de publicação:
2014
Tipo de documento:
Article