Omeprazole Theophylline

Other Formulations. Neural networks have been applied to the modeling of pellet formulations to control the release of theophylline [63] and to control the rate of degradation of omeprazole [64]. They have also been applied to the preparation of acrylic microspheres [65] and to model the release of insulin from an implant [66]. In arecent study from Brazil, the release of hydrocortisone from a biodegradable matrix has been successfully modeled [67]. 

While generally not of major concern, omeprazole may inhibit the metabolism of warfarin, diazepam, and phenytoin lansoprazole may decrease theophylline concentrations. Drug interactions with omeprazole are of particular concern in patients who are considered slow metabolizers, as are approximately 3% of the Caucasian population. Unfortunately, it is unclear which patients have the polymorphic gene variation that makes them slow metabolizers.17 The metabolism of esomeprazole may also be altered in patients with this polymorphic gene variation. Patients on potentially interacting drugs should be monitored for development of drug-related problems. 

Substrates Inhibitors Inducers CYP1A2 Acetaminophen, caffeine, clozapine, imipramine, theophylline, propranolol Most fluoroquinolone antibiotics, fluvoxamine, cimetidine Tobacco smoking, charcoal-broiled foods, cruciferous vegetables, omeprazole... 

CYP1A2 Theophylline, unipramine Omeprazole, tobacco smoke Fluvoxamine, furafyUine... 

GFJ has been shown to increase the exposure of carbamazepine (175), cisapride (176-179), fluvoxamine (184), losartan (188), methadone (189), scopolamine (191), and sertraline (192). However, only the interaction of GFJ with carbamazepine and cisapride seems to be clinically relevant. No alteration in exposure was observed for clozapine (180,181), heophylline (195), halo-peridol (196), and omeprazole (190). Reports of increased pharmacokinetic parameters of clozapine, theophylline, and haloperidol suggest that an interaction is unlikely to be clinically relevant. Contradicting results were reported for itraconazole (185-187), digoxin (75,183), and sildenafil (193,194). An increased effect on concomitant use of diclofenac and GFJ was observed in rats (182). Overall, the clinical relevance for this drug class appears to be low. 

Omeprazole can inhibit the metabolism of drugs metabolised mainly by the cytochrome P-450 enzyme subfamily 2C (diazepam, phenytoin), but not of those metabolished by subfamilies lA (caffeine, theophylline), 2D (metoprolol, propranolol), and 3A (ciclosporin, lidocaine (lignocaine), quinidine). Since relatively few drugs are metabolised mainly by 2C compared with 2D and 3A, the potential for omeprazole to interfere with the metabolism of other drugs appears to be limited, but the half lives of diazepam and phenytoin are prolonged as much as by cimetidine. 

A2 Acetaminophen, antipyrine, caffeine, clomipramine, phenacetin, tacrine, tamoxifen, theophylline, warfarin Smoking, charcoal-broiled foods, cruciferous vegetables, omeprazole Galangin, furafylline, fluvoxamine... 

A2 Tertiary amine TCAs, duloxetine, theophylline, phenacetin, TCAs (demethylation), clozapine, diazepam, caffeine Fluvoxamine, fluoxetine, moclobemide, ramelteon Tobacco, omeprazole... 

CIMETIDINE FAMOTIDINE NIZATIDINE, RANITIDINE BRONCHODILATORS -THEOPHYLLINE t efficacy and adverse effects, including seizures. There is conflicting information associated with ranitidine, famotidine and nizatidine Inhibition of metabolism via CYP1A2, cimetidine being the best known inhibitor Use alternative acid suppression, e.g. a proton pump inhibitor (not omeprazole or lansoprazole) or monitor closely considerable patient variation. Check levels on day 3 and then at 1 week. A 30-50% i dose of theophylline may be required. For doses <400 mg/day, the interaction may not be clinically significant... 

Acetaminophen, aldrin, alfentanil, amiodarone, aminopyrine, amitriptyline, amprenavir, androstenedione,antipyrine, astemizole, benzphetamine, budesonide, carbamazepine, celecoxib, chlorpromazine, chlorzoxazone, cisapride, clarithromycin, clozapine, cocaine, codeine, cortisol, cyclophosphamide,cyclosporin, dapsone, delavirdine, dextromethorphan, digitoxin, diltiazem, diazepam, erythromycin, 17j3-estradiol, ethinylestradiol, etoposide, felbamate, fentanyl, flutamide, hydroxyarginine, ifosphamide, imipramine, indinavir, ketoconazole, lansoprazole, loratidine, losartan, lovastatin, (iS)"mephen3d in, methadone, mianserin, miconazole, mifepristone, nelfinavir, nevirapine, nicardipine, nifedipine, odansetron, omeprazole, orphenadrine, proguanil, propafenone, quinidine, quinine, rapamycin, retinoic acid, ritonavir, saquinavir, selegiline, serindole, sufentanil, sulfinpyrazone, tacrolimus, tamoxifen, tamsulosin, taxol, teniposide, terfenadine, tetrahydrocannabinol, theophylline, toremifene, triazolam, trimethadone, trimethoprim, troleandomycin, verapamil, warfarin, zatosetron, Zolpidem, zonisamide... 

CYP1A2 15 -5 Fluvoxamine Caffeine Cyclobenzaprine Theophylline Thiothixene Olanzapine Ciprofloxacin Fluvoxamine Ticlopidine Halogenated biphenyls Polycyclic aromatic Hydrocarbons Omeprazole Rosiglitazone Phenylisothiocyanate... 

Metoprolol Midazolam Naproxen Nifedipine Omeprazole Ondansetron Orphenadrine Phenytoin Piroxicam Progesterone Propafenone Propranolol Quinidine Rifampin Sibutramine Sildenafil Simvastatin Tacrine Tamoxifen Terfenadine Testosterone Theophylline Timolol Tolbutamide Tramadol Triazolam Verapamil Warfarin (R) Warfarin (S) Zolmitriptan Zolpidem... 

CYP1A2 caffeine, imipramine, paracetamol, theophylline cigarette smoke, omeprazole cimetidine, ciprofloxacin, enoxacin, fluvoxamine... 

A2 Benzo[a]pyrene (from tobacco smoke), carbamazepine, phenobarbital, rifampin, omeprazole Acetaminophen, clozapine, haloperidol, theophylline, tricyclic antidepressants. (R)-warfarin... 

Omeprazole may cause a small increase in theophylline clearance, and lansoprazole may canse a small decrease in theophylline levels, neither of which are likely to be clinically relevant Pantopra-zole and rabeprazole do not appear to interact with theophylline. 

The changes in the half-life and clearance of theophylline caused by omeprazole were found to be small and clinically unimportant in two studies. No changes in the steady-state pharmacokinetics of theophylline were found in other studies. However, one study found that omeprazole produced an 11% increase in the clearance of theophylline in poor metabolisers of omeprazole (i.e. those with low levels of the cytochrome P450 isoenzyme CYP2C19 and therefore higher levels of omeprazole), but this seems unlikely to be clinically significant. 

Oosterhuis B, Jonkman JHG, Andersson T, Zuiderwijk PBM. No influence of single intravenous doses of omeprazole on theophylline elimination kinetics. J Clin Pharmacol (1992) 32, 470-5. 

Sommers De K, van Wyk M) Snyman JR, Moncrieff J. The effects of omeprazole-induced hypochlorhydria on absorption of theophylline from a sustained-release formulation. EurJ Clin Pharmacol (1992) A3, 141-3. 

Taburet AM, Geneve J, Bocquentin M, Simoneau G, Caulin C, Singlas E. Theophylline steady state pharmacokinetics is not altered by omeprazole. EurJ Clin Pharmacol (1992) 42, 343-5. 

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