Evaluation of a pantoprazole and 4-desmethylpantoprazole-sulfate metabolic ratio as a novel CYP2C19 phenotyping method
Abstract
Aims: CYP2C19 is one of the most important pharmacogenes, and its activity is highly variable due to factors such as genetics or drug-drug interactions. Due to the lack of an appropriate endogenous CYP2C19 biomarker, surrogate methods to assess its activity are warranted. The aim of this work was to validate pantoprazole as a CYP2C19 phenotyping drug.
Methods: We performed a single-dose pharmacokinetic study with 20 healthy participants in a randomized cross-over design. Participants received 10 mg omeprazole and 20 mg pantoprazole on two different study days with a washout phase of one week. Blood sampling was performed at 14 time points spanning 8 h after drug administration. Drug and metabolite plasma concentrations were assessed by LC-MS/MS. Metabolic ratios (MR) of metabolite/substrate were formed using the area under the curve from 0 to 8 h (AUC0-8h) and single plasma concentrations.
Results: We demonstrate very strong correlations (Spearman ρ = 0.84) of AUC0-8h MR 4-desmethylpantoprazole-sulfate/pantoprazole to the validated CYP2C19 probe AUC0-8h MR 5-hydroxyomeprazole/omeprazole (Spearman ρ = 0.84). Single time point pantoprazole MRs measured in plasma between 4 and 8 h after pantoprazole administration were sufficient for accurate CYP2C19 phenotyping by demonstrating significant and robust correlations to the AUC0-8h MR 5-hydroxyomeprazole/omeprazole with Spearman ρ ≥ 0.8.
Conclusions: In contrast to omeprazole, pharmacokinetics of pantoprazole are described to be…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 20 participants or records.
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