Warfarin Diclofenac

Tolbutamide methylhydroxylation Phen5rtoin 4-hydroxylation (iS)Warfarin 7-hydroxylation> Rifampin Dexamethasone Tienilic acid" Warfarin Diclofenac... 

FIGURE 4.11 Structures of the CYP2C9 substrates, warfarin, tolbutamide, (S (-flurbiprofen, and diclofenac, and their metabolites. 

Figure 9.3 The effects of varying levels of accessory proteins on CYP2C9 kinetics using diclofenac (a) or (S)-warfarin (b) as substrate probe [219].

Acenocoumarol, amiodarone, celecoxib, coumadin, dexamethasone, diclofenac, etoposide, fluconazole, fluoxetine, fluvas-tatin, fluvoxamine, ghmepiride, ghpizide, glyburide, ibuprofen, irbesartan, isoniazid, losartan, midazolam, phenylbutazone, phenytoin, rifampin, teniposide, tenoxicam, thiotepa, tolbutamide, torsemide, vitamin D, warfarin... 

Drugs that may be affected by HMG-CoA reductase inhibitors include oral contraceptives, diclofenac, digoxin, glyburide, phenytoin, and warfarin. Atorvastatin, lovastatin, and simvastatin are primarily metabolized by CYP3A4 they may interact with CYP3A4 inhibitors. 

D pharmacophore models for competitive inhibitors of CYP2C9 were built using Catalyst (173). Three different metabolic reactions, diclofenac 4 -hydroxylation, (S)-warfarin 7-hydroxylation, and tolbutamide 4-hydroxylation, were considered. The general characteristics of the three models were similar with distances between a hydrogen bond acceptor and a second hydrogen bond acceptor/donor being 3.4—5.7 A and the hydrophobic feature was positioned... 

C9 Tienilic acid, tolbutamide, warfarin, phenytoin, THC, hexobarbital, diclofenac [Diclofenac (4 -OH)]... 

Yamazaki H, Inoue K, Chiba K, et al. Comparative studies on the catalytic roles of cytochrome P450 2C9 and its Cys- and Leu-variants in the oxidation of warfarin, flurbiprofen, and diclofenac by human liver microsomes. Biochem Pharmacol 1998 56 243-251. 

CYP2C9 Liver Intestine CYP2C9 2 CYP2C9 3 (S)-warfarin C6-, C7 hydroxylation (preferred1) Diclofenac 4 -hydroxylation (acceptable1) Tolbutamide para CH3-hydroxylation (acceptable1) Sulfaphenazole (preferred1) Rifampicine Phenobarbital 15-20 %... 

Probe drugs used for CYP2C9 phenotyping are tolbutamide, S-warfarin, phenytoin and losartan. Diclofenac, flurbiprofen, phenprocoumone and torasemide have also been used. For safety concerns, the current preferred probe is tolbutamide, despite some risk of hypoglycemia. 

Diclofenac 50 mg prn Need to change to different pain control as high risk of bleeding when on warfarin and aspirin. Must not be taken as required. 

Figure 17.4 Compounds which are mentioned throughtout the chapter and numbered in the main text as follows (1) DMZ, (2) diclofenac, (3) flurbiprofen, (4) warfarin, (5) fluconazole, (6) coumarin, (7) dapsone, (8) retinoic acid, (9) arachidonic acid, (10) troglitazone, (11) fluvastatin, (12) cerivastatin, (13) taxol, (14) gemfibrozil, (15) verapamil, (16) amodiaquine, (17) amiodarone, (18) metyrapone, (19) progesterone, (20) testosterone, (21) erythromycin, (22) ketoconazole, (23) nicotine, (24) IV -Nitrosonor-nicotine, (25) 4-(Methylnitrosamino)-l-(3-pyridyl)-l-butanone...

CYP2C9 Diclofenac Hexobarbital I bu profen Naproxen Phenytoin Tolbutamide S-Warfarin... 

CYP2C9 20 10 Celecoxib Diclofenac Fluoxetine Fluvastatin Ibuprofen Irbesarten Naproxen Amitriptyline Phenytoin Tolbutamide Torsemide S-warfarin Rosiglitazone Amiodarone Fluconazole Fluvoxamine Fluvastatin Isoniazid Sertraline Sulfaphenazole Trimethoprin Zafirlukast Rifampin Clotrimazole Carbamazepine Hyperforin Phenobarbital Ritonavir... 

Also analyzed acebutolol, acepromazine, acetaminophen, acetazolamide, acetophenazine, albuterol, amitriptyline, amobarbital, amoxapine, antipsrrine, atenolol, atropine, azata-dine, baclofen, benzocaine, bromocriptine, brompheniramine, brotizolam, bupivacaine, buspirone, butabarbital, butalbital, caffeine, carbamazepine, cetirizine, chlorqyclizine, chlordiazepoxide, chlormezanone, chloroquine, chlorpheniramine, chlorpromazine, chlorpropamide, chlorprothixene, chlorthalidone, chlorzoxazone, cimetidine, cisapride, clomipramine, clonazepam, clonidine, clozapine, cocaine, codeine, colchicine, qyclizine, (yclo-benzaprine, dantrolene, desipramine, diazepam, diclofenac, diflunisal, diltiazem, diphenhydramine, diphenidol, dipheno late, dipyridamole, disopyramide, dobutamine, doxapram, doxepin, droperidol, encainide, ethidium bromide, ethopropazine, fenoprofen, fentanyl, flavoxate, fluoxetine, fluphenazine, flurazepam, flurbiprofen, fluvoxamine, fii-rosemide, glutethimide, glyburide, guaifenesin, haloperidol, homatropine, hydralazine, hydrochlorothiazide, hydrocodone, hydromorphone, hydro g chloroquine, hydroxyzine, ibuprofen, imipramine, indomethacin, ketoconazole, ketoprofen, ketorolac, labetalol, le-vorphanol, lidocaine, loratadine, lorazepam, lovastatin, loxapine, mazindol, mefenamic acid, meperidine, mephenytoin, mepivacaine, mesoridazine, metaproterenol, methadone, methdilazine, methocarbamol, methotrexate, methotrimeprazine, methoxamine, methyl-dopa, methylphenidate, metoclopramide, metolazone, metoprolol, metronidazole, midazolam, moclobemide, morphine, nadolol, nalbuphine, naloxone, naphazoline, naproxen, nifedipine, nizatidine, norepinephrine, nortriptyline, oxazepam, oxycodone, oxymetazo-line, paroxetine, pemoline, pentazocine, pentobarbital, pentoxifylline, perphenazine, pheniramine, phenobarbital, phenol, phenolphthalein, phentolamine, phenylbutazone, phenyltoloxamine, phenytoin, pimozide, pindolol, piroxicam, pramoxine, prazepam, prazosin, probenecid, procainamide, procaine, prochlorperazine, procyclidine, promazine, promethazine, propafenone, propantheline, propiomazine, propofol, propranolol, protriptyline, quazepam, quinidine, quinine, racemethorphan, ranitidine, remoxipride, risperidone, salicylic acid, scopolamine, secobarbital, sertraline, sotalol, spironolactone, sulfinpyrazone, sulindac, temazepam, terbutaline, terfenadine, tetracaine, theophylline, thiethyl-perazine, thiopental, thioridazine, thiothixene, timolol, tocainide, tolbutamide, tolmetin, trazodone, triamterene, triazolam, trifluoperazine, triflupromazine, trimeprazine, trimethoprim, trimipramine, verapamil, warfarin, xylometazoline, yohimbine, zopiclone... 

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