A02BC01 - Omeprazole |
Not porphyrinogenic |
NP |
Rationale
Only a weak, and clinically insignificant inducer of CYP 3A4. A very large number of reports of carriers of acute porphyria tolerating omeprazol and there are no reports of porphyric side effects among them.
Chemical description
(RS)-5-Methoxy-2-(4-methoxy-3,5-dimethyl-2-pyridylmethylsulphinyl)benzimidazole. M =345.4.
Therapeutic characteristics
Omeprazole is a proton pump inhibitor. It suppresses secretion of gastric acid by inhibiting the enzyme system of hydrogen/potassium adenosine triphosphatase (H+/K+ ATPase), the proton pump of the gastric parietal cell. It is used in dyspepsia, gastro-oesophageal reflux disease, peptic ulcer disease and other. Although adverse effects of proton pump inhibitors are relatively infrequent, there has been reported some adverse reactions that can mimic porphyria symptoms such as fatigue, constipation, abdominal pain, nausea and vomiting.
Hepatic exposure
Probably significant in poor metabolizers of CYP 2C19.
Metabolism and pharmakokinetics
Omeprazole is extensively metabolised, mainly by CYP2C19, only to a small extent by CYP3A4 and CYP2D6. Omeprazol is an inhibitor of CYP 2C19. It is also a weak inhibitor of CYP 3A4 and CYP 2C9, but in vitro studies in human liver microsomal preparations has shown that the inhibition of 3A4 and 2C9 is weak and competitive (Ko et al 1997, Li et al 2004). Therefore it is not of relevance in acute porphyria. There are no known drug interactions with omeprazole in vivo that involves CYP 3A4 or 2C9. Clinically significant inhibitor of CYP 2C19 metabolism. Three per cent of caucasions are poor metabolizers of CYP 2C19 and thus have higher blood concentrations of omeprazole.
Personal communication
Thunell, patient reports (n=16): tolerated. C.Andersson; patient reports: tolerated (n=5)
IPNet drug reports
Uneventful use reported in 98 patients with acute porphyria.
References
- Scientific articles
- Ko JW et al. Evaluation of omeprazole and lansoprazole as inhibitors of cytochrome P450 isoforms. Drug Metab Dispos 1997. #3266
- Li XQ et al. Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities, Drug Metab Dispos 2004. #3267
- Drug reference publications
- Martindale 2009 #3265
Similar drugs
© NAPOS 2024