Imipramine Verapamil

PAMPA-pKa fiux optimized design (pOD)-permeabiiity Iso-pH mapping unstirred PAMPA was used to measure the effective permeability, Pe, as a function of pH from 3 to 10, of five weak monoprotic acids (ibuprofen, naproxen, ketoprofen, salicylic acid, benzoic acid), an ampholyte (piroxicam), five monoprotic weak bases (imipramine, verapamil, propranolol, phenazopyridine, metoprolol), and a diprotic weak base (quinine). The intrinsic permeability, Po, the UWL permeability, Pu, and the apparent pKa (pKa.fiux) were determined from the pH dependence of log Pg. The underlying permeability-pH equations were derived for multiprotic weak acids, weak bases, and ampholytes. The average thickness of the UWL on each side of the membrane was estimated to be nearly 2000 p, somewhat larger than that found in Caco-2 permeability assays (unstirred). As the UWL thickness in the human intestine is believed to be about forty times smaller, it is critical to correct the in vitro permeability data for the effect of the UWL. Without such correction, the in vitro permeability coefficient of lipophilic molecules would be indicative only of the property of water. In single-pH PAMPA (e.g., pH 7.4), the uncertainty of the UWL contribution can be minimized if a specially selected pH (possibly different from 7.4) were used in the assay. From the analysis of the shapes of the log Pe-pH plots, a method to improve the selection of the assay pH, called pOD-PAMPA, was described and tested. From an optimally selected assay pH, it is possible to estimate Pg, as well as the entire membrane permeability-pH profile. 

Membrane retention of lipophilic molecules is significantly increased in octanol, compared to 2% DOPC. Chlorpromazine and progesterone show R > 90% in octanol. Phenazopyridine, verapamil, promethazine, and imipramine show R > 70%. 

VERAPAMIL DILTIAZEM PROMETHAZINE PHENAZOPYRIDINE DESIPRAMINE PROGESTERONE IMIPRAMINE CHLORPROMAZINE GRISEOFULVIN PROPRANOLOL CARBAMAZEPINE QUININE IBUPROFEN PIROXICAM PRIMAQUINE CAFFEINE ANTIPYRINE METOPROLOL NAPROXEN KETOPROFEN SULPIRIDE TERBUTALINE FUROSEMIDE SULPHASALAZINE RANITIDINE HYDROCHLOROTHIAZIDE ATENOLOL AMIOLORIDE... 

Imipramine (Tofranil) [Antidepressant/TCA] WARNING Close observation for suicidal thinking or unusual changes in behavior Uses Depres-sion, enuresis, panic attack, chronic pain Action TCA t CNS synaptic serotonin or norepinephrine Dose Adults. Hospitalized Initial 100 mg/24 h PO in doses T over several wk 300 mg/d max Output Maint 50-150 mg PO hs, 300 mg/24 h max Peds. Antidepressant 1.5-5 mg/kg/24 h daUy-qid Enuresis >6 y 10-25 mg PO qhs T by 10-25 mg at 1-2-wk int vals (max 50 mg for 6-12 y, 75 mg for >12 y) Rx for 2-3 mo, then tap Caution [D, /-] Contra Use w/ MAOIs, NAG, acute recovery from MI, PRG, CHF, angina, CVD, arrhythmias Disp Tabs, caps SE CV Sxs, dizziness, xerostomia, discolored urine Interactions t Effects W/ amiodarone, anticholinergics, BBs, cimetidine, diltiazem, Li, OCPs, quinidine, phenothiazines, ritonavir, verapamil, EtOH, evening primrose oil t effects OF CNS depressants, hypoglycemics, warfarin T risk of serotonin synd W/MAOIs 4-... 

Cimetidine Lidocaine, propranolol, verapamil, imipramine Increased absorption... 

CALCIUM CHANNEL BLOCKERS TCAs t plasma concentrations of TCAs when co administered with diltiazem and verapamil. Reports of cardiotoxicity (first- and second-degree block) when imipramine is given with diltiazem or verapamil Uncertain, but may be due to a combination of i clearance of TCAs (both diltiazem and verapamil are known to inhibit CYP1A2, which has a role in the metabolism of amitriptyline, clomipramine and imipramine) and t intestinal absorption (diltiazem and verapamil inhibit intestinal P-gp, which may t amitriptyline bioavailability) Monitor ECG when commencing or altering treatment... 

CANNABIS AMITRIPTYUNE, CLOMIPRAMINE, DESIPRAMINE, IMIPRAMINE, NORTRIPTYLINE t risk of tachycardia. Heart rate may t to 100-160 beats per minute, with some records of 300 beats per minute resistant to verapamil therapy Additive antimuscarinic effect Ask patients about cannabis use if they present with otherwise unexplained tachycardias while taking these drugs... 

Buspirone Imipramine Propranolol Verapamil SYR110155 SYR110180 SYR110182 SYR110184... 

Octnl (Slc22a4) Rat TEA, MPP+ DMA, nicotine Drugs cimetidine, desipramine, imipramine, procainamide, verapamil... 

Clinically important, potentially hazardous interactions with acebutolol, amitriptyline, amoxapine, atenolol, betaxolol, carteolol, clomipramine, desipramine, dexmethylphenidate, doxepin, esmolol, imipramine, insulin detemir, insulin glulisine, metoprolol, nadolol, nortriptyline, oxprenolol, penbutolol, pindolol, propranolol, protriptyline, sulpiride, timolol, tricyclic antidepressants, trimipramine, verapamil... 

Acetaminophen, acetanilide, aminopyrine, antipyrine, aromatic amines, chlorzoxazone, clozapine, 17/3-estradiol, flutamide, imipramine,lidocaine,((S)-and (i )-mianserin, (S)- and (J )-naproxen, phenacetin, propafenone, tacrine, tamoxifen, theophylline, trimethadone, verapamil, (7 )-warfarin, zolpidem... 

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... 

Also analyzed amiodarone, clomipramine, desipramine, haloperidol, imipramine, propafenone, verapamil... 

Also analyzed acebutolol, acetaminophen, alprazolam, amphetamine, atenolol, betaxolol, brotizolam, caffeine, camazepam, captopril, chloroquine, clobazam, clomipramine, cloth-iapine, clotiazepam, cloxazolam, cocaine, codeine, clofenac, dihydralazine, dihydrocodeine, dihydroergotamine, diphenhydramine, domperidone, doxepin, droperidol, ergota-mine, ethyl lodazepate, fenethylline, fluoxetine, flupentixol, flurazepam, furosemide, gliclazide, hydrochlorothiazide, hydroxyzine, ibuprofen, imipramine, ketazolam, loprazo-1am, lorazepam, lormetazepam, maprotiline, medazepam, mepyramine, methadone, methaqualone, methyldopa, methylphenidate, metoclopramide, metoprolol, mexiletine, mianserin, midazolam, minoxidil, morphine, nadolol, nitrazepam, oxprenolol, papaverine, pentazocine, phenprocoumon, phenylbutazone, pipamperone, piritramide, practolol, pra-zepam, prazosin, promazine, promethazine, propoxyphene, propranolol, prothipendyl, quinine, sotalol, sulpride, thioridazine, trazodone, triazolam, trimipramine, tripelennamine, t5Tamine, verapamil, yohimbine... 

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