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Proton pump inhibitors (PPIs) are extensively metabolized in the liver by CYP2C19, that demonstrates genetic polymorphism with 21 mutant alleles. The subjects can be divided into 2 groups with respect to CYP2C19 phenotypes viz., extensive metabolizers (EMs) and poor metabolizers (PMs) of PPIs. This division results in marked interindividual variations in the pharmacokinetics and pharmacodynamics of PPIs in the population. Intragastric pH values and the plasma concentration of PPIs after oral ingestion were significantly lower in EMs namely normal homozygotes (CYP2C19*1/*1) and heterozygotes (CYP2C19*1/*X) compared to PMs namely mutant homozygotes (CYP2C19*X/*X) where 'X' represents the mutant allele. Hence, association has been found between the genetic polymorphism of CYP2C19 and therapeutic response to PPIs. CYP2C19 polymorphism affected eradication of Helicobacter pylori using diferent PPI based eradication therapies as PM patients demonstrated significantly higher eradication rates compared to EMs. CYP2C19 genetic polymorphism also affects the therapeutic outcome of gastroesophageal reflux disease (GERD), reflux oesophagitis and duodenal ulcers. For optimal therapeutic response with PPIs, CYP2C19 pharmacogenetics should be taken into consideration. This shall help in the prescription of optimal doses of PPIs, thus paving the way for personalized medication.
Key words CYP2C19 - Helicobacter pylori - pharmacogenetics - proton pump inhibitors
Cytochromes P450 (CYPs) are the drug metabolizing enzymes found primarily in the liver. Inter-individual variations in the metabolism of drugs have been observed in different ethnic groups due to the occurrence of genetic polymorphism of the drug metabolizing enzymes. Genetic polymorphism is the occurrence of a variant allele with a frequency of 1 per cent or greater in a population. Although various allelic forms of different CYPs have been reported, functional polymorphism has only been established for CYP2A6, CYP2C9, CYP2C19 and CYP2D61. On the basis of genetic polymorphism a population may be divided into two groups namely extensive metabolizers (EMs) demonstrating normal metabolism of the drugs and poor metabolizers (PMs) demonstrating impaired metabolism of drugs due to the deficiency of CYPs. The first PM of mephenytoin, a probe drug for CYP2C19, was reported by Kupfer et al in 19792. Subsequently the genetic basis of CYP2C19 PM trait was demonstrated3,4. Omeprazole (OPZ)5 and proguanil6 are the other probe drugs used to assess the activity of CYP2C19. Subjects having a log hydroxylation index value more than 1.7...