Most PPIs are subject to metabolism by CYP2C19 polymorphism, and the CYP2C19 metabolizer status of the majority of whites (-84%), blacks (>90%), and Asians (—100%) can be determined by genotyping only two variant alleles, CYP2C19*2 and CYP2C19*3, as described above.
Desta and colleagues have explored the economic utility of CYP2C19 geno-typing for the treatment of peptic ulcer disease with PPIs.33 Assuming treatments of 3 months for extensive metabolizers, 2 months for intermediate metabolizers, and 1 month for poor metabolizers, and a conservative genotyping cost saving of U.S. $10 per allele, they estimated a cost saving of equal or greater than U.S. $5000 per 100 Asian patients genotyped. Because of differences in the frequencies of CYP2C19 alleles, the cost:benefit ratio for prospective gene-based prescribing might be quite different in white and black populations. Despite lower minor allele frequencies in non-Asian populations, CYP2C19 might still lead to improved, cost-effective care. Since Helicobactor pylori eradication rates in homozygous (—80%) and heterozygous (-98%) extensive metabolizers and poor metabolizers (—100%) differ significantly,68,69 and since extensive metabolizers have lower eradication rates, Lehmann et al. postulated that gene-based therapy would be cost effective if extensive metabolizers were given a regimen containing anti-H. pylori treatment and an H2-histamine receptor blocker (ranitidine) instead of a PPI.70 Lehmann et al. predicted a breakeven cost of approximately U.S. $90-119 per genotype on implementing CYP2C19-based testing for non-Asian patients within the United States. For Pacific Rim (Asian) patients, they found the cost savings of CYP2C19 genotyping was greater (U.S. $495-2195).
Savings are relatively modest in this example, but it should be recognized that the PPIs as a class have a wide therapeutic index. Hence, the potential savings might be amplified for drugs with a narrower safety margin, particularly for drugs with clinically severe toxicity. Warfarin is such an example and is considered below.
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