Ibuprofen Propranolol

The above-described oral-input-related changes in enantiomeric ratios in the plasma for ibuprofen, propranolol, etodolac, and verapamil have been documented only after administration of the IR and CR formulations or after oral input rates that differ substantially. An important issue that needs to be addressed is what if the two formulations compared are CR formulations whose input rate differences are not that substantial Can a relatively small difference between the rate of release/dissolution produce significant changes in the concentrations of the active enantiomer that cannot be detected by measurement of the total drug concentration ... 

Most of the chiral membrane-assisted applications can be considered as a modality of liquid-liquid extraction, and will be discussed in the next section. However, it is worth mentioning here a device developed by Keurentjes et al., in which two miscible chiral liquids with opposing enantiomers of the chiral selector flow counter-currently through a column, separated by a nonmiscible liquid membrane [179]. In this case the selector molecules are located out of the liquid membrane and both enantiomers are needed. The system allows recovery of the two enantiomers of the racemic mixture to be separated. Thus, using dihexyltartrate and poly(lactic acid), the authors described the resolution of different drugs, such as norephedrine, salbu-tamol, terbutaline, ibuprofen or propranolol. 

Allopurinol, barbiturates, carbamazepine, cephalosporins, cyclophosphamide, ethambutol, fluconazole, ibuprofen, lamotrigine, macrolides, nitrofurantoin, penicillins, phenytoin, propranolol, quinolones, sulfonamide antimicrobials, sulindac, tetracyclines, thiazides, valproic acid, and vancomycin... 

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... 

Ibuprofen-1-naphthyl-amide, benzoic acid 1 -phenylethylamide, 1 - (1 -naphthyl) ethyl -phenylurea, sulfoxides, propranolol oxazo-lidin-2-one] and others (S)-N- 3,5 -dinitro -benzoyl) tyrosine derivatives -Heptane, 207 2-propanol and diethylamine mixtures... 

For highly potent APIs, profound effects can occur at low ng levels, the adverse effect of ethynylestradiol on fish populations is one example [107]. Another example is the development of resistant bacterial strains induced by the release of antibiotics into the environment [112, 113]. Dome et al. [114] concluded that fluoxetine, ibuprofen, diclofenac, propranolol and metoprolol exhibit relatively high acute toxicity to aquatic species. In addition, due to the inherent properties of these chemicals, pharmacodynamic effects were observed in the heart rate of Daphnia magna for the (3-blockers propranolol and metoprolol. 

Figure 1.30. LC-MS/MS (MRM) chromatograms of (a) propranolol (260—>116)/ketoconazole (531 489) and (b) diclofenac (294, 250)/ibuprofen (205. 161) in rat plasma obtained with online SPE and either a Luna C18 column (left panels) or a Chromolith monolithic column (right panels) combination. (Reprinted with permission from Alnouti et at., 2005.)...

Sotalol, metoprolol, propranolol, carvedilol, nifedipine, captopril, cilazapril, milrinone, ticlopidine, acenocoumarol, furosemide, acetylsalicylic acid, salicylic acid, ibuprofen, naproxen, ketoprofen, diclofenac, paracetamol, dipyrone, mildronate, sildenafil, dexa-methasone, carbamazepine, terbinafine/urine UHPLC MS/MS Column Zorbax Rapid Resolution High Definition SB-C18 (50 x 2.1 mm, 1.8 pm) Mobile phase Solvent A 0.1 % HCOOH in water Solvent B MeOH (gradient elution) Detection MS/MS, ionization ESI Protein precipitation LOQ 0.05-0.60 ng/mL [71]... 

Aliskiren, prasugrel, rivaroxaban, prednisolone, propranolol, ketoprofen, nifedipine, naproxen, terbinafine, ibuprofen, diclofenac, sildenafil, acenocoumarol/urine UHPLC UV Column Poroshell 120EC-Ci8 (100 X 3.0 mm 2.7 pm) Mobile phase Solvent A 0.05 % TFA in water Solvent B ACN (gradient elution) Detection 2 = 221, 228, 230, 240, 250, 275, 280 nm Extraction SPE/column CgHs/elution MeOH LOD 0.003-0.217 pg/mL LOQ 0.01-0.650 pg/mL [75]... 

Four basic, three acidic, and one neutral SAs including propranolol and ibuprofen Chiral AGP [2441... 

For the clinical pharmacologist, neither of these racemic drug mixtures is problematic for drug therapy in the clinic if a pharmacodynamic endpoint (e.g., decrease in blood pressure with propranolol or improvement in arthritic pain with ibuprofen) is used to establish drug dose. However, to effectively characterize the pharmacokinetics of the active isomer, an endeavor that may be useful during drug development, administration, and/or specific determination of the active isomer is required. Such data... 

It is expected that the method is not specific to atenolol but is effective for other compounds as well. This possibility was investigated by studying its effectiveness on other types of compounds including two drugs (ibuprofen and propranolol) and two amino acids (alanine and phenylalanine). Figure 3 A-D show the results obtained where the calculated concentrations are plotted... 

Figure 3. Predicted enantiomeric composition versus actual composition for 60 mM of (A) ibuprofen (B) atenolol (C) phenylalanine and (D) alanine in S-CI ITA TI tN ionic liquid. Filled circles, S-enantiomers for ibuprofen and propranolol and L-enantiomers for phenylalanine and alanine Open circles, R-enantiomers for propranolol and D-enantiomers for phenylalanine and alanine.

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. 

Many drug compounds are racemic mixtures of stereoisomers. In most cases, one of the isomers is more pharmacologically active than the other isomer, and each isomer may exhibit different pharmacokinetic properties. Warfarin, propranolol, verapamil, and ibuprofen are aU racemic mixtures of stereoisomers. Some drug interactions inhibit or increase the elimination of only one stereoisomer. The importance of the drug interaction depends on which isomer is affected. Other drugs, such as dextromethorphan, levofloxacin, and dUtiazem, are composed of just one stereoisomer. 

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 acebutolol, acetaminophen, alprazolam, amphetamine, atenolol, betaxolol, brotizolam, caffeine, camazepam, captopril, chloroquine, clobazam, clomipramine, cloth-iapine, clotiazepam, cloxazolam, cocaine, codeine, diclofenac, dihydralazine, dihydrocodeine, dihydroergotamine, diphenhydramine, domperidone, doxepin, droperidol, ergota-mine, ethyl loflazepate, fenethylline, fluoxetine, flupentixol, flurazepam, furosemide, gliclazide, hydrochlorothiazide, hydroxyzine, ibuprofen, imipramine, ketazolam, loprazo-1am, lorazepam, lormetazepam, maprotUine, 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, lyramine, verapeunil, yohimbine... 

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