To study on the effect of CYP2C19 gene polymorphism on the efficacy of PPI or clopidogrel, and analyze the drug-drug interaction of coadministration of PPI and other drugs in the elderly.

The samples of 100 elderly patients, ranged from 75 to 97 years old, who were hospitalized in Department of Geriatrics Huashan hospital Fudan University from March 2014 to January 2015 were included. All patients took standard dose of PPI qd and/or clopidogrel 75 mg qd regularly. CYP2C19 genotype was indentified by microarray method. pH of their succus gastricus was measured, platelet inhibition rate of clopidogrel was determined by thromboelastogram (TEG), and maximum platelet aggregation rate was determined by light transmittance aggregometry (LTA). Kai-square test was applied to analyze the Hardy-Weinberg balance of CYP2C19 genes among patients. ANOVA test was utilized to compare among multiple groups, andt-test was further used to dertermined differences between two groups.

Extensive, intermediate, and poor metabolism groups were 42, 46, and 12 samples respectively. PPI only, clopidogrel only, and PPI+clopidogrel were 16, 14, and 12 samples respectively in extensive metabolism group; 22, 10, and 14 in intermediate metabolism group; 4, 4, and 4 in poor metabolism group. Distribution of CYP2C19 alleles was accorded with Hardy-Weinberg balance (χ²=0.49,P>0.05). No differences of age, gender, blood cells count, hepatic and renal functions, proBNP, and blood glucose among groups (P>0.05). There were difference of platelet inhibition rate in patients taken PPI only in different metabolism groups were (76.3±13.1)%, (55.9±19.1)%, and (29.9%±6.1)%,(F=14.82,P<0.05). In patients taken clopidogrel only, platelet inhibition rate were (76.3±13.1)%, (55.9±19.1)%, and (29.9%±6.1)%, and PAG(M) were (33.2±12.1)%, (35.2±13.8)%, and (65.4±8.3)%. Both of them have significant differences (F=14.82, 10.02,P<0.05 or 0.01). Gastric pH values in PPI+clopidogrel groups were 3.66±0.7, 4.5±0.5, and 5.0±0.7 respectively. Platelet inhibition rate were (67.3±12.7)%, (40.6±25.8)%, and (3.9±4.3)%. PAG(M) were (36.3±11.3)%, (56.2±24.0)%, and (75.5%±12.3)%. All these data have significant differences (F=9.33, 15.46, 7.08,P<0.05 or 0.01). No difference of gastic pH values between PPI+clopidogrel and PPI only in extensive metabolism group; and no difference of platelet inhibition rate and PAG(M) between in PPI+clopidogrel and clopidogrel only patients in extensive metabolism group (t=-0.15,-1.70, 0.67,P>0.05). In intermediate metabolism group, no differences of gastic pH between PPI+clopidogrel and PPI only groups (t=0.41,P > 0.05), and no difference of platelet inhibition rate in PPI+clopidogrel and clopidogrel groups (t=-1.05,P > 0.05), but only PAG(M) of PPI+clopidogrel and clopidogrel groups have significant diffrence [(56.2±24.0)%, (35.2±13.8)%,t=2.38,P<0.05]. In poor metabolism group, no difference of gastric pH values between PPI+clopidogrel and PPI only groups; and no difference of PAG(M) between PPI+clopidogrel and clopidogrel only groups (t=-0.13, 1.18,P>0.05), but only PPI+clopidogrel and clopidogrel groups have difference of platelet inhibition rate [(3.9±4.3)%, (29.9±6.1)%,t=-6.06,P<0.05]. Gastric pH values in patients using CYP450 metabolic mediations, CYP450 inhibitors, and non-CYP450 metabolic mediations were 4.2±0.8, 4.9±0.7, and 3.9±0.9 (F=3.12, P<0.05).

In the elderly, the polymorphism of CYP2C19 gene impacts on both the acid inhibition of PPI and anti-platelet activity of clopidogrel. Coadministration of PPI and clopidogrel may affect their effects. CYP450 inhibitors affect the gastric acid inhibition of PPI when they were coadministrated.