Terfenadine Acetaminophen

A4 Acetaminophen, alfentanil, amiodarone, astemizole, cocaine, cortisol, cyclosporine, dapsone, diazepam, dihydroergotamine, dihydropyridines, diltiazem, ethinyl estradiol, gestodene, indinavir, lidocaine, lovastatin, macrolides, methadone, miconazole, midazolam, mifepristone (RU 486), paclitaxel, progesterone, quinidine, rapamycin, ritonavir, saquinavir, spironolactone, sulfamethoxazole, sufentanil, tacrolimus, tamoxifen, terfenadine, testosterone, tetrahydro-cannabinol, triazolam, troleandomycin, verapamil Barbiturates, carbamazepine, macrolides, glucocorticoids, pioglitazone, phenytoin, rifampin Erythromycin, 613-hydroxy cortisol... 

In the discovery phase, metabolite identification is usually performed with a combination of in vitro and in vivo experiments using samples from different species in order to compare metabolite exposures. The structural identification of major circulating metabolites formed in nonclinical animal models as well as the metabolites formed in human in vitro systems is needed for the metabolites to be synthesized and their pharmacological activities and/or toxicological implications to be determined [25], In addition, metabolite identification can lead to the discovery of candidates with satisfactory clearance/PK properties and/or improved safety profile. Following are some examples of metabolites that were later developed as drugs desloratadine from loratadine, acetaminophen from phenacetin, morphine from codeine, minoxidil sulfate from minoxidil, fexofenadine from terfenadine, and oxazepam from diazepam. 

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... 

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... 

Cimetidine 1.2 g daily for 5 days had no effect on the pharmacokinetics of a single 120-mg dose of terfenadine in 12 healthy subjects. Another study in two groups of 6 healthy subjects confirmed that cimetidine 600 mg every 12 hours or ranitidine 150 mg every 12 hours had no effect on the pharmacokinetics of terfenadine 60 mg every 12 hours. No adverse ECG changes were seen. However, an isolated case report describes a 63-year-old woman who had 8 episodes of syncope (later identiiied as being due to torsade de pointes) and a convulsion 2 days after starting terfenadine 60 mg twice daily and cimetidine 400 mg twice daily. She was also taking chiorphenamine and co-proxamol (paracetamol (acetaminophen) and dextropropoxyphene (propoxyphene)). ... 

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