Evaluation of lansoprazole as a probe for assessing cytochrome P450 2C19 activity and genotype-phenotype correlation in childhood.

PURPOSE

Lansoprazole, a cytochrome P450 2C19 (CYP2C19) substrate, has been widely used in children to manage acid-related diseases. CYP2C19 exhibits marked genetic polymorphisms, and distribution of these polymorphisms varies among different ethnic groups. There is limited data regarding the use of probe drugs for determining CYP2C19 activity in children. The aim of this study was to evaluate lansoprazole as an in vivo phenotyping probe for assessing CYP2C19 activity in children.

METHODS

The CYP2C19*2, *3, and *17 variants were determined in 244 children. Three hours after a single oral dose of lansoprazole (n = 94) or omeprazole (n = 19), plasma lansoprazole and 5-hydroxy lansoprazole or omeprazole and 5-hydroxy omeprazole concentrations were analyzed by high-performance liquid chromatography.

RESULTS

The CYP2C1917 was the most frequent variant allele (24.4%). The group of patients with CYP2C191717 genotype had a 70% lower (p < 0.05) mean lansoprazole plasma concentration compared with the CYP2C1911 genotype group, whereas the CYP2C192*2 group had 6.9-fold higher (p < 0.01) mean lansoprazole plasma concentration. Lansoprazole metabolic ratios (lansoprazole/5-hydroxy-lansoprazole) were found to be significantly lower in the 1717 [mean ± standard deviation (SD); 2.8 ± 2.1] group and higher in the 22 group (63.5 ± 12.2) compared with that of the 11 genotype group (6.1 ± 4.5).

CONCLUSION

According to our results from a Turkish pediatric population, lansoprazole is a suitable probe drug for phenotyping CYP2C19. The CYP2C19*2 and *17 variants should be taken into consideration in predicting the clinical outcome of therapy with lansoprazole in the pediatric population.