Relationship between the acid-suppression efficacy of proton pump inhibitors and CYP2C19 genetic polymorphism in patients with peptic ulcer

Objective To investigate acid-suppression efficacy of proton pump inhibitors(PPIs) in relation to CYP2C19 genetic polymorphism on patients with peptic ulcer. Methods By an open, randomized and control trial, fifty nine patients with active peptic ulcer were randomly assigned to receive one of three PPIs on a single dose (20 mg of each drug): omeprazole group (n=19), rabeprazole group (n=20) and esomeprazole group (n=20). Intragastric pH was recorded 1 hour before and 24 hours after administration. CYP2C19 genotype was tested in all patients. Results The EMs/PMs ratio of each group was 16/3,17/3 and 17/3, respectively. The total time that intragastric pH>4, time percent pH>4 and median pH in PMs patients were significantly higher than those in EMs patients of omeprazole group (P<0.05). But all these differences were not found in rabeprazole group and esomeprazole group. The pH of nocturnal acid breakthrough(NAB) in both rabeprazole group and esomeprazole group was higher than that of omeprazole group, while there was no significant difference between rabeprazole group and esomeprazole group.Conclusion The acid-suppression efficacy of omeprazole is highly dependent on CYP2C19 genetic polymorphism, while CYP2C19 genetic polymorphism may have a little influence on the acid-suppression efficacy of rabeprazole and esomeprazole. The acid-suppression action of rabeprazole and esomeprazole is superior to omeprazole, especially on night acid secretion.

Risk of fracture and pneumonia from acid suppressive drugs

A recently published systematic review and meta-analy-sis, incorporating all relevant studies on the association of acid suppressive medications and pneumonia identi-fied up to August 2009, revealed that for every 200 patients, treated with acid suppressive medication, one will develop pneumonia. They showed the overall risk of pneumonia was higher among people using proton pump inhibitors （PPIs） [adjusted odds ratio （OR） = 1.27, 95% CI： 1.11-1.46, I2 = 90.5%] and Histamine-2 re-ceptor antagonists （H2RAs） （adjusted OR = 1.22, 95% CI： 1.09-1.36, I2 = 0.0%）. In the randomized controlled trials, use of H2RAs was associated with an elevated risk of hospital-acquired pneumonia （relative risk 1.22, 95% CI： 1.01-1.48, I2 = 30.6%）. Another meta-analysis of 11 studies published between 1997 and 2011 found that PPIs, which reduce stomach acid production, were associated with increased risk of fracture. The pooled OR for fracture was 1.29 （95% CI： 1.18-1.41） with use of PPIs and 1.10 （95% CI： 0.99-1.23） with use of H2RAs, when compared with non-use of the respective medications. Long-term use of PPIs increased the risk of any fracture （adjusted OR = 1.30, 95% CI： 1.15-1.48） and of hip fracture risk （adjusted OR = 1.34, 95% CI： 1.09-1.66）, whereas long-term H2RA use was not sig-nifcantly associated with fracture risk. Clinicians should carefully consider when deciding to prescribe acid-sup-pressive drugs, especially for patients who are already at risk for pneumonia and fracture. Since it is unneces-sary to achieve an achlorhydric state in order to resolve symptoms, we recommend using the only minimum effective dose of drug required to achieve the desired therapeutic goals.