Dataset Information

Is (+)-[13C]-pantoprazole better than (±)-[13C]-pantoprazole for the breath test to evaluate CYP2C19 enzyme activity?

ABSTRACT: Recently, we have shown that the (+)-[(13)C]-pantoprazole is more dependent on CYP2C19 metabolic status than (-)-[(13)C]-pantoprazole. In this study, we tested the hypothesis that (+)-[(13)C]-pantoprazole is a more sensitive and selective probe for evaluating CYP2C19 enzyme activity than the racemic mixture. (+)-[(13)C]-pantoprazole (95 mg) was administered orally in a sodium bicarbonate solution to healthy volunteers. Breath and plasma samples were collected before and up to 720 min after dosing. The (13)CO2 in exhaled breath samples was measured by infrared spectrometry. Ratios of (13)CO2/(12)CO2 after (+)-[(13)C]-pantoprazole relative to (13)CO2/(12)CO2 at baseline were expressed as delta over baseline (DOB). (+)-[(13)C]-pantoprazole concentrations were measured by HPLC. Genomic DNA extracted from whole blood was genotyped for CYP2C19*2, *3 and *17 using Taqman assays. Statistically significant differences in the area under the plasma concentration time curve (AUCplasma(0-?) (p < 0.001) and oral clearance (<0.01) of (+)-[(13)C]-pantoprazole as well as in the breath test indices (delta over baseline, DOB30; and area under the DOB versus time curve, AUCDOB(0-120)) (p < 0.01) were observed among poor, intermediate and extensive metabolizer of CYP2C19. DOB30 and AUCDOB(0-120) adequately distinguished poor metabolizer from intermediate and extensive metabolizer of CYP2C19. Breath test indices significantly correlated with plasma elimination parameters of (+)-[(13)C]-pantoprazole (Pearson correlations: -0.68 to -0.73). Although relatively higher breath test indices were observed after administration of (+)-[(13)C]-pantoprazole (this study) than after (±)-[(13)C]-pantoprazole (previous study), the performance of the racemic and the enantiomer as marker of CYP2C19 activity remained similar. Our data confirm that the metabolism of (+)-[(13)C]-pantoprazole is highly dependent on CYP2C19 metabolic status, but the breath test derived from it is not superior to the racemic [(13)C]-pantoprazole in evaluating CYP2C19 activity in vivo. Thus, racemic [(13)C]-pantoprazole which is relatively easy to synthesize and more stable than (+)-[(13)C]-pantoprazole is adequate as a probe of this enzyme.

SUBMITTER: Thacker DL

PROVIDER: S-EPMC3587180 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Is (+)-[13C]-pantoprazole better than (±)-[13C]-pantoprazole for the breath test to evaluate CYP2C19 enzyme activity?

Thacker David L DL Modak Anil A Flockhart David A DA Desta Zeruesenay Z

Journal of breath research 20121221 1

Recently, we have shown that the (+)-[(13)C]-pantoprazole is more dependent on CYP2C19 metabolic status than (-)-[(13)C]-pantoprazole. In this study, we tested the hypothesis that (+)-[(13)C]-pantoprazole is a more sensitive and selective probe for evaluating CYP2C19 enzyme activity than the racemic mixture. (+)-[(13)C]-pantoprazole (95 mg) was administered orally in a sodium bicarbonate solution to healthy volunteers. Breath and plasma samples were collected before and up to 720 min after dosin ...[more]

PMID: 23257668

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Project description:Helicobacter pylori (H. pylori) can cause gastritis, peptic ulcer diseases and gastric carcinoma. Endoscopy as the gold standard method of diagnosis is an invasive procedure that might not be suitable in all scenarios. Therefore, this first study in Jordan aimed to assess the non-invasive 13C urea breath test (UBT) and stool antigen test for diagnosis of H. pylori infection and the successfulness of eradication therapy as alternatives for endoscopy. Hence, a total of 30 patients attending the endoscopy units at Alkarak teaching hospital were asked to complete a questionnaire with demographic and clinical data. They were then tested for H. pylori using 13C UBT and H. pylori stool antigen before having endoscopy. Another 30 patients who were positive for H. pylori by endoscopy were tested using both tests 6 weeks post eradication therapy. Results showed that the rate of H. pylori detection using endoscopy was 56.7% (17/30). Heartburns (82.3%, p value = 0.019), epigastric pain (88.2%, p value = 0.007) and vomiting (70.5%, p value = 0.02) were the most significant symptoms. Family history of peptic ulcer diseases was significantly associated with an increased risk for having a H. pylori positive result (p value = 0.02). Compared to endoscopy, the sensitivity of 13C UBT for the diagnosis of H. pylori was 94.1% (16/17), while it was 76.5% (13/17) for the stool antigen test. The specificity of both tests was equal (76.9%). However, the positive predictive and negative predictive values (84.2% and 90.9%) for 13C UBT were higher than those (81.3% and 71.4%) for the stool antigen test. The accuracy of 13C UBT was 86.7% compared to 76.7% for the stool antigen test. There was an 87% agreement (20 patients out of 23) between both tests when used to assess success of the eradication therapy. In conclusion, the 13C UBT was found to be more sensitive and accurate than the stool antigen test when used for diagnosis; furthermore, it has a comparable outcome to the stool antigen test in assessing the successfulness of the eradication treatment.

Dataset Information

Is (+)-[13C]-pantoprazole better than (±)-[13C]-pantoprazole for the breath test to evaluate CYP2C19 enzyme activity?

Publications

Is (+)-[13C]-pantoprazole better than (±)-[13C]-pantoprazole for the breath test to evaluate CYP2C19 enzyme activity?

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