AI Article Synopsis
- Pharmacokinetic variability in drug exposure is an important issue for asthma treatments like GSK2190915, a drug that inhibits certain inflammatory compounds.
- A study involving 41 patients showed that genetic variations UGT1A1*28 and UGT1A3*2 were linked to the drug's oral clearance, suggesting these genes could influence how the drug is processed.
- However, a larger follow-up study with 403 patients did not find a significant connection between these genetic factors and drug clearance, indicating that other explanations for the drug's variable effects may be needed.
Article 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=3.8×10⁻⁴ and 1.2×10⁻⁵, 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.
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| http://dx.doi.org/10.1097/FPC.0000000000000090 | DOI Listing |
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