Omeprazole treatment does not affect the metabolism of caffeine.

This study was performed to investigate the possible influence of repeated omeprazole dosing on the metabolism of caffeine, which has been shown to reflect the activity of one specific enzyme within the hepatic cytochrome P450 family, P450IA2. Ten healthy, nonsmoking young men participated in this placebo-controlled double-blind trial. Each subject was given omeprazole, 20 mg, every morning for 1 week and placebo every morning for 1 week in random order and separated by a 2-3 week washout period. On the sixth and seventh days of each period urine was collected twice daily, and urinary metabolites of caffeine were determined by high-performance liquid chromatography. The urinary metabolite ratio of three paraxanthine 7-demethylation products relative to a paraxanthine-hydroxylation product corresponds to caffeine clearance and, therefore, to P450IA2 activity. This calculated ratio was 4.8 (95% confidence interval, 3.9-5.6) in the placebo and 4.6 (95% confidence interval, 3.6-5.5) in the omeprazole period. These results show that the metabolism of caffeine was unaltered following omeprazole treatment, indicating that omeprazole treatment has no influence on cytochrome P450IA2 activity in the clinical situation.

[1]  J. Miners,et al.  Characterisation of theophylline metabolism by human liver microsomes. Inhibition and immunochemical studies. , 1988, Biochemical pharmacology.

[2]  A. Richens,et al.  Oral phenytoin pharmacokinetics during omeprazole therapy. , 1987, British journal of clinical pharmacology.

[3]  S. Spielberg,et al.  A urinary metabolite ratio that reflects systemic caffeine clearance , 1987, Clinical pharmacology and therapeutics.

[4]  G. Porro,et al.  A comparison of two different doses of omeprazole versus ranitidine in treatment of duodenal ulcers. , 1986, Journal of clinical gastroenterology.

[5]  J. Bridges,et al.  The relationship between the binding of 2-n-alkylbenzimidazoles to rat hepatic microsomal cytochrome P-450 and the inhibition of monooxygenation. , 1982, Biochemical pharmacology.

[6]  T. Leemann,et al.  Single-dose quinidine treatment inhibits metoprolol oxidation in extensive metabolizers , 2004, European Journal of Clinical Pharmacology.

[7]  R. Branch,et al.  Propranolol's metabolism is determined by both mephenytoin and debrisoquin hydroxylase activities , 1989, Clinical pharmacology and therapeutics.

[8]  F. Gonzalez,et al.  The molecular biology of cytochrome P450s. , 1988, Pharmacological reviews.

[9]  R. Gugler,et al.  Omeprazole inhibits oxidative drug metabolism. Studies with diazepam and phenytoin in vivo and 7-ethoxycoumarin in vitro. , 1985, Gastroenterology.

[10]  M. Butler,et al.  Human cytochrome P-450PA (P-450IA2), the phenacetin O-deethylase, is primarily responsible for the hepatic 3-demethylation of caffeine and N-oxidation of carcinogenic arylamines. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[11]  J. Dent,et al.  Healing and relapse of severe peptic esophagitis after treatment with omeprazole. , 1988, Gastroenterology.

[12]  P. Watkins,et al.  Distribution of cytochromes P-450, cytochrome b5, and NADPH-cytochrome P-450 reductase in an entire human liver. , 1990, Biochemical pharmacology.

[13]  M. J. Coon,et al.  The P450 superfamily: updated listing of all genes and recommended nomenclature for the chromosomal loci. , 1989, DNA.

[14]  M. Classen,et al.  Effect of omeprazole and ranitidine on ulcer healing and relapse rates in patients with benign gastric ulcer. , 1989, The New England journal of medicine.

[15]  A. Boobis,et al.  Furafylline is a potent and selective inhibitor of cytochrome P450IA2 in man. , 1990, British journal of clinical pharmacology.

[16]  V. Marks,et al.  Determination of the urinary metabolites of caffeine and theophylline by high-performance liquid chromatography. A comparative study of a direct injection and an ion-pair extraction procedure. , 1986, Journal of chromatography.

[17]  S. Devenish-Meares,et al.  Propranolol steady-state pharmacokinetics are unaltered by omeprazole , 2004, European Journal of Clinical Pharmacology.

[18]  R. Edwards,et al.  A form of cytochrome P450 in man, orthologous to form d in the rat, catalyses the O-deethylation of phenacetin and is inducible by cigarette smoking. , 1988, British journal of clinical pharmacology.

[19]  H. Larsson,et al.  The mechanism of action of omeprazole--a survey of its inhibitory actions in vitro. , 1985, Scandinavian journal of gastroenterology. Supplement.

[20]  L. Bertilsson,et al.  Importance of genetic factors in the regulation of diazepam metabolism: Relationship to S‐mephenytoin, but not debrisoquin, hydroxylation phenotype , 1989, Clinical pharmacology and therapeutics.

[21]  S. Loft,et al.  Cytochrome P450 IA2 activity in man measured by caffeine metabolism: effect of smoking, broccoli and exercise. , 1991, Advances in experimental medicine and biology.

[22]  U. Haglund,et al.  Effect of omeprazole--a gastric proton pump inhibitor--on pentagastrin stimulated acid secretion in man. , 1983, Gut.

[23]  K. Brøsen,et al.  Mephenytoin and sparteine oxidation: genetic polymorphisms in Denmark. , 1989, British journal of clinical pharmacology.

[24]  B K Tang,et al.  Variability in caffeine metabolism , 1983, Clinical pharmacology and therapeutics.

[25]  P. Maurel,et al.  Omeprazole is an aryl hydrocarbon-like inducer of human hepatic cytochrome P450. , 1990, Gastroenterology.

[26]  K. Anderson,et al.  Enhanced phenacetin metabolism in human subjects fed charcoal‐broiled beef , 1976, Clinical pharmacology and therapeutics.

[27]  G. Tucker,et al.  Oxidation phenotype--a major determinant of metoprolol metabolism and response. , 1982, The New England journal of medicine.

[28]  J. Miners,et al.  Relationship between phenytoin and tolbutamide hydroxylations in human liver microsomes. , 1991, British journal of clinical pharmacology.

[29]  D. Grant,et al.  Effect of allopurinol on caffeine disposition in man. , 1986, British journal of clinical pharmacology.

[30]  P. Lagerström,et al.  Determination of omeprazole and metabolites in plasma and urine by liquid chromatography. , 1984, Journal of chromatography.

[31]  R. Gugler,et al.  Omeprazole inhibits oxidative drug metabolism , 1985 .

[32]  L. Bertilsson,et al.  Slow omeprazole metabolizers are also poor S-mephenytoin hydroxylators. , 1990, Therapeutic drug monitoring.

[33]  T. Andersson,et al.  A Study of the Interaction Between Omeprazole and Phenytoin in Epileptic Patients , 1990, Therapeutic drug monitoring.

[34]  R. Gugler,et al.  Drugs other than H2-receptor antagonists as clinically important inhibitors of drug metabolism in vivo. , 1987, Pharmacology & therapeutics.