Influence of different proton pump inhibitors on activity of cytochrome P450 assessed by [(13)C]-aminopyrine breath test
| Autor: | Akira Hishida, Noriyuki Namiki, Mitsushige Sugimoto, Takahisa Furuta, Mutsuhiro Ikuma, Hiroshi Watanabe, Shinya Uchida, Mihoko Yamade, Masafumi Nishino, Chise Kodaira |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Genotype medicine.drug_class Rabeprazole Lansoprazole Proton-pump inhibitor CYP2C19 Pharmacology 2-Pyridinylmethylsulfinylbenzimidazoles Young Adult medicine Humans Pharmacology (medical) Aminopyrine Omeprazole Breath test Carbon Isotopes medicine.diagnostic_test biology Chemistry Cytochrome P450 Proton Pump Inhibitors Anti-Ulcer Agents Cytochrome P-450 CYP2C19 Oral ingestion Breath Tests Area Under Curve biology.protein Female Aryl Hydrocarbon Hydroxylases medicine.drug Half-Life |
| Zdroj: | Journal of clinical pharmacology. 52(3) |
| ISSN: | 1552-4604 |
| Popis: | Aminopyrine is metabolized by cytochrome P450 (CYP) in the liver. The investigators evaluated influences of different PPIs on CYP activity as assessed by the [(13)C]-aminopyrine breath test ([(13)C]-ABT). Subjects were 15 healthy volunteers with different CYP2C19 status (5 rapid metabolizers [RMs], 5 intermediate metabolizers [IMs], and 5 poor metabolizers [PMs]). Breath samples were collected before and every 15 to 30 minutes for 3 hours after oral ingestion of [(13)C]-aminopyrine 100 mg on day 8 of each of the following regimens: control; omeprazole 20 mg and 80 mg, lansoprazole 30 mg, and rabeprazole 20 mg. Changes in carbon isotope ratios in carbon dioxide ((13)CO(2)/(12)CO(2)) in breath samples were measured by infrared spectrometry and expressed as delta-over-baseline (DOB) ratios (‰). Mean areas under the curve of DOB from 0 to 3 h (AUC(0-3h) of DOB) were significantly decreased by omeprazole 20 mg and lansoprazole 30 mg but not by rabeprazole 20 mg. Conversely, higher PPI dose (ie, omeprazole 80 mg) seemed to further decrease AUC(0-3h) of DOB in RMs but increased it in PMs. Omeprazole and lansoprazole at the standard doses inhibit CYP activity but rabeprazole does not, whereas high-dose omeprazole seems to induce CYPs. |
| Databáze: | OpenAIRE |
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