Effect of CYP2C19 Polymorphism on Treatment Success in Lansoprazole-Based 7-Day Treatment Regimen for Cure of H. pylori Infection in Japan

Recently, Helicobacter pylori (H. pylori)-positive peptic ulcer patients were treated by a 1-week triple therapy [lansoprazole (LPZ) 30 mg, amoxicillin 750 mg and clarithromycin 200 or 400 mg, each twice daily] without the checking CYP2C19 genotype in Japan. This regimen was done to obtain sufficient cure rates for H. pylori infection using a high dose of LPZ (60 mg/day) without the great cost of having to determine the genotype. However, the failure rate for eradicating H. pylori was reported to be 12.5%. The reasons for this were studied in 33 Japanese patients with H. pylori-positive gastric or duodenal ulcer. Blood samples of the patients were collected to determine the genotype of CYP2C19 and plasma concentrations of LPZ and its metabolites at 3 h postdose on the morning of the 7th day of treatment. H. pylori infection was cured in 25 of the 33 patients (75.8%). The cure rate was highest in the group of poor metabolizers (PM), intermediate in the group of extensive metabolizers of the heterozygous type (htEM) and lowest in the group of extensive metabolizers of the homozygous type (hmEM). The relative ratio of mean plasma concentration for LPZ among the 3 groups was 1.00:1.43:2.93 (hmEM:htEM:PM groups). Our data suggest that success of the eradication is dependent on the CYP2C19-related genotypic status or the plasma concentrations of LPZ in a steady state condition after a multiple dosing regimen; that is to say, checking CYP2C19 is necessary even on occasions when treatment is done by H. pylori eradication methods as performed in Japan

Negative and positive control ranges in the bacterial reverse mutation test: JEMS/BMS collaborative study

Abstract A large-scale study was conducted by multiple laboratories affiliated with the Japanese Environmental Mutagen Society and the Bacterial Mutagenicity Study Group to investigate possible proficiency indicators for the bacterial reverse mutation test with a preincubation procedure. Approximately 30 laboratories generated negative and positive control count data and dose-response curves of the positive control articles for the bacterial reverse mutation test, with assays conducted annually from 2013 to 2016. Overall, the majority of the negative and positive control counts for Salmonella Typhimurium strains TA100, TA1535, TA98, and TA1537, and Escherichia coli strain WP2uvrA, with and without S9 mix, were within the range of the means ±2× standard deviation. The negative counts were normally distributed (strains TA100, TA98, and WP2uvrA) or followed Poisson distribution (strains TA1535 and TA1537), and the positive control counts for all strains were approximately normally distributed. In addition, the distribution of the negative and positive control counts was relatively constant over the 4 years. The number of revertant colonies increased in a dose-dependent linear or exponential fashion up to the recommended doses for the respective positive control articles in Japan. These data are valuable for determining the acceptance criteria and an estimation of the laboratory proficiency for the bacterial reverse mutation test

Additional file 6: of Negative and positive control ranges in the bacterial reverse mutation test: JEMS/BMS collaborative study

Figure S5. Dose-response curves of revertant Escherichia coli strain WP2uvrA colonies following treatment with AF-2 in the absence of S9 mix (a), or with 2AA in the presence of S9 mix (b). Individual dose-response curves were generated using results produced by each participating laboratory in 2016 (different colors indicate different laboratories). The doses tested were 0.0025, 0.005, and 0.01 μg/plate for AF-2, and 2.5, 5.0, and 10 μg/plate for 2AA. (ODP 342 kb

Additional file 3: of Negative and positive control ranges in the bacterial reverse mutation test: JEMS/BMS collaborative study

Figure S2. Dose-response curves of revertant Salmonella Typhimurium strain TA98 colonies following treatment with AF-2 in the absence of S9 mix (a), or treatment with 2AA in the presence of S9 mix (b). Individual dose-response curves were generated using results produced by each participating laboratory in 2016 (different colors indicate different laboratories). The doses tested were 0.025, 0.05, and 0.1 μg/plate for AF-2, and 0.125, 0.25, and 0.5 μg/plate for 2AA. (ODP 434 kb

Additional file 1: of Negative and positive control ranges in the bacterial reverse mutation test: JEMS/BMS collaborative study

Table S1. Positive control articles and their doses used in this study (DOCX 18 kb

Additional file 5: of Negative and positive control ranges in the bacterial reverse mutation test: JEMS/BMS collaborative study

Figure S4. Dose-response curves of revertant Salmonella Typhimurium strain TA1537 colonies following treatment with 9AA in the absence of S9 mix (a), or with 2AA in the presence of S9 mix (b). Individual dose-response curves were generated using results produced by each participating laboratory in 2016 (different colors indicate different laboratories). The doses tested were 20, 40, and 80 μg/plate for 9AA, and 0.5, 1.0, and 2.0 μg/plate for 2AA. (ODP 343 kb

Additional file 2: of Negative and positive control ranges in the bacterial reverse mutation test: JEMS/BMS collaborative study

Figure S1. Dose-response curves of revertant Salmonella Typhimurium strain TA100 colonies following treatment with AF-2 in the absence of S9 mix (a), or with 2AA in the presence of S9 mix (b). Individual dose-response curves were generated using results produced by each participating laboratory in 2016 (different colors indicate different laboratories). The doses tested were 0.0025, 0.005, and 0.01 μg/plate for AF-2, and 0.25, 0.5, and 1.0 μg/plate for 2AA. (ODP 423 kb

Additional file 4: of Negative and positive control ranges in the bacterial reverse mutation test: JEMS/BMS collaborative study

Figure S3. Dose-response curves of revertant Salmonella Typhimurium strain TA1535 colonies following treatment with SA in the absence of S9 mix (a), or with 2AA in the presence of S9 mix (b). Individual dose-response curves were generated using results produced by each participating laboratory in 2016 (different colors indicate different laboratories). The doses tested were 0.125, 0.25, and 0.5 μg/plate for SA, and 0.5, 1.0, and 2.0 μg/plate for 2AA. (ODP 411 kb