Association of CYP2C19 polymorphisms and lansoprazole-associated respiratory adverse effects in children.
Association of CYP2C19 polymorphisms and lansoprazole-associated respiratory adverse effects in children.
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DOI：
10.1016/j.jpeds.2013.03.017
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发表时间：
2013-09
期刊：
影响因子：
--
通讯作者：
Teague WG
中科院分区：
文献类型：
--
作者：
Lima JJ;Lang JE;Mougey EB;Blake KB;Gong Y;Holbrook JT;Wise RA;Teague WG
To determine whether cytochrome P450 (CYP)2C19 haplotype associates with lansoprazole-associated adverse event frequency. Respiratory adverse events from a clinical trial of lansoprazole in children with asthma were analyzed for associations with extensive or poor metabolizer (PM) phenotype based on CYP2C19 haplotypes. Carriers of CYP2C19*2, *3, *8, or *9 alleles were PMs; carriers of 2 wild-type alleles were extensive metabolizers (EMs). Plasma concentrations of lansoprazole were determined in PM and EM phenotypes. The frequency of upper respiratory infection among PMs (n = 45) was higher than that among EMs (n = 91), which in turn was higher than that in placebo subjects (n = 135; P = .0039). The frequency of sore throat (ST) was similarly distributed among EMs and PMs (P = .0015). The OR (95% CI) for upper respiratory infections in PMs was 2.46 (1.02–5.96) (P = .046); for EMs, the OR (95% CI) was 1.55 (0.86–2.79). The OR (95% CI) for ST in EMs and PMs was 2.94 (1.23–7.05, P = .016) vs 1.97 (1.09–3.55, P = .024), respectively. Mean ± SD plasma concentrations of lansoprazole were higher in PMs than in EMs: 207 ± 179 ng/mL vs 132 ± 141 ng/mL (P = .04). Lansoprazole-associated upper respiratory infections and ST in children are related in part to CYP2C19 haplotype. Our data suggest that lansoprazole-associated adverse events in children may be mitigated by adjusting the conventional dose in PMs. Additional studies are required to replicate our findings.
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