Troleandomycin

Sample preparation Inject a 10 iaL aliquot of a 40 mg/mL solution in MeCN. 

Mobile phase MeCN 200 mM pH 6.0 anunonium acetatenvater 45 5 50 Flow rate 1 Injection volume 10 Detector UV 205 

Chepkwony, H.K. Roets, E. Hoogmsirtens, J. Liquid chromatography of troleandomycin, J.Chro-matogr.A, 2001, 914, 53-58. 

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Ester derivatives of oleandomycia (17, R = CH ) were also pursued leading to commercial development of (31) also known as troleandomycin (TOA), which improved oral bioavadabihty and taste as compared to the parent (135). 

Therapeutic Function Antibiotic Chemical Name Oleandomycin see Structural Formula Common Name Troleandomycin Structural Formula ... 

Tetracyclines. It is important to give the tetracyclines on an empty stomach tetracyclines are not to be taken with dairy products (milk or cheese). The exceptions are doxycycline (Vibramycin) and minocycline (Minocin), which may be taken with dairy products or food. The nurse should give clindamycin with food or a full glass of water. The nurse can give troleandomycin and clarithromycin without regard to meals. All tetracyclines should be given with a full glass of water (240 mL). 

CYP450 In vitro studies show significant inhibition of the formation of the active metabolite of losartan by inhibitors of cytochrome P450 3A4 (eg, ketoconazole, troleandomycin) or P450 2C9 (sulfaphenazole). The consequences of concomitant use of losartan and these inhibitors have not been examined. 

All patients with the following conditions Serum potassium greater than 5.5 mEq/L at initiation Ccr 30 mL/min or less concomitant use with the following potent CYP3A4 inhibitors Ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, and nelfinavir. 

Pregnancy (ergotamine s powerful uterine stimulant actions may cause fetal harm) hypersensitivity to ergot alkaloids peripheral vascular disease (eg, thromboangiitis obliterans, leutic arteritis, severe arteriosclerosis, thrombophlebitis, Raynaud s disease) hepatic or renal impairment severe pruritus coronary artery disease hypertension sepsis. The use of potent CYP3A4 inhibitors (ritonavir, nelfinavir, indinavir, erythromycin, clarithromycin, troleandomycin, ketoconazole, itraconazole) with dihydroergotamine is contraindicated. 

Drugs that may affect aprepitant include CYP 3A4 inhibitors (eg, clarithromycin, diltiazem, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, troleandomycin), CYP3A4 inducers (eg, carbamazepine, phenytoin, rifampin), and paroxetine. 

Pimozide Drugs that prolong the QT interval - CYP3A inhibitors (eg, clarithromycin, dirithromycin, erythromycin, itraconazole, ketoconazole, nefazodone, protease inhibitors, sertraline, telithromycin, troleandomycin, voriconazole)... 

Drugs that can increase carbamazepine serum levels include cimetidine, danazol, diltiazem, erythromycin, felbamate, clarithromycin, fluoxetine, isoniazid, niacinamide, propoxyphene, ketaconazole, itraconazole, verapamil, valproate, troleandomycin, loratadine, nicotinamide, tricyclic antidepressants, SSRIs, nefazodone, protease inhibitors. 

Drugs that may increase sirolimus blood concentrations include the following Nicardipine, verapamil, clotrimazole, fluconazole, itraconazole, clarithromycin, erythromycin, troleandomycin, cisapride, metoclopramide, bromocriptine, cimetidine, danazol, HIV-protease inhibitors, cyclosporine, diltiazem, azole antifungals. 

Aprepitant (Emend) [Centrally Acting Antiemetic] Uses Pre-vents N/V assoc w/ emetogenic CA chemo (eg, cisplatin) (use in combo w/ other antiemetics) Action Substance P/neurokinin l(NKi) receptor antagonist Dose 125 mg PO day 1, 1 h before chemo, then 80 mg PO qAM days 2 3 Caution [B, /-] Contra Use w/ pimozide, Disp Caps SE Fatigue, asthenia, hiccups Interactions T Effects W/ clarithromycin, diltiazem, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, troleandomycin T effects OF alprazolam, astem-izole, cisapride, dexamethasone, methylprednisolone, midazolam, pimozide, terfe-nadine, triazolam, chemo agents, eg, docetaxel, etoposide, ifosfamide, imatinib, irinotecan, paclitaxel, vinblastine, vincristine, vinorelbine i effects W/ paroxetine,... 

Prednisolone [Corticosteroid] [See Steroids and Table VI-1] Interactions T Effects W/ clarithromycin, erythromycin, estrogen, ketoconazole, OCPs, troleandomycin X effects W/ antacids, aminoglutethimide, barbiturates, cholestyramine, colestipol, phenytoin, rifampin X effects OF anticoagulants, hypoglycemics, INH, salicylates, vaccine toxoids EMS Infxns may be masked OD May cause wt gain, T hair growth, acne, HTN, peripheral edema, and sore muscles symptomatic and supportive... 

Uses Chronic asthma Actions Topical steroid Dose Two inhalations tid-qid or 4 inhal bid Caution [C, ] Contra Component aU gy Disp Met-dose inhaler SE Cough, oral candidiasis Interactions T Risk of GI bleed W/ ASA, NSAIDs T effects W/ sakneterol, troleandomycin -1- effects W/barbiturates, hydantoins, pheny-toin, rifampin T effects OF diuretics, insulin, oral hypoglycemics, K supl, salicylates, somatrem, live virus vaccines EMS May affect glucose(hyperglycemia) monitor ECG for hypokalemia (flattened T waves) concurrent ASA/NSAID use may t risk of GI bleeding OD Acute OD unlikely to cause life-threatening Sxs, chronic OD may lead to S/Sxs of muscle weakness, and osteoporosis symptomatic and supportive... 

Macrolide-type antibiotics Clarithromycin, erythromycin, telithromycin, troleandomycin Opioids Alfentanyl, cocaine, fentanyl, sufentanil Steroids Budesonide, cortisol, 17- 3-estradiol, progesterone... 

Others Acetaminophen, amiodarone, carbamazepine, delavirdine, efavirenz, nevirapine, quinidine, repaglinide, sildenafil, tadalafil, trazodone, vardenafil Amiodarone, amprenavir, atazanavir, ciprofloxacin, cisapride, clarithromycin, diltiozem, erythromycin, fluconazole, fluvoxamine, grapefruit juice (in high ingestion), indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, norfloxacin, ritonavir, telithromycin, troleandomycin, verapamil, voriconazole Carbamazepine, efavirenz, glucocorticoids, macrolide antibiotics, nevirapine, phenytoin, phenobarbital, rifabutin, rifapentine, rifampin, St. John s wort... 

Robimycin), clarithromycin (Biaxin), azithromycin (Zithwmax), and oleandomycin (Matwmycin). Erythromycin and its derivatives (clarithromycin, azithromycin) are the only macrolides in common use, although the acetylated derivative of oleandomycin (troleandomycin, TAO) is available for oral use. 

Nefazodone substantially decreases the clearance rate for triazolam, which results in a 400% increase in triazolam s serum levels (131). Erythromycin can also interfere with the metabolism of triazolam, resulting in decreased clearance and increased plasma levels, possibly causing toxicity. Troleandomycin and other macrolide antibiotics, such as clarithromycin, flurithromycin, josamycin, midecamycin, or roxithromycin, also may inhibit triazolam s metabolism (132). The coadministration of itraconazoie and triazolam can produce a marked elevation of triazolam plasma levels associated with statistically significant impairment of psychomotor tests and a prolongation of other effects (e.g., amnesia, lethargy, and confusion) for hours after awakening ( 133). 

With the important exception of additive effects when combined with other CNS depressants, including alcohol, BZDs interact with very few drugs. Disulfiram (see the section The Alcoholic Patient in Chapter 14) and cimetidine may increase BZD blood levels, and diazepam may increase blood levels of digoxin and phenytoin. Antacids may reduce the clinical effects of clorazepate by hindering its biotransformation to desmethyidiazepam. Coadministration of a BZD and another drug known to induce seizures may possibly increase seizure risk, especially if the BZD is abruptly withdrawn. Furthermore, as noted earlier, important interactions have been reported among nefazodone, erythromycin, troleandomycin, and other macrolide antibiotics, as well as itraconazole. In each case, metabolism is inhibited, and triazolam levels can increase significantly. 

Warot D, Bergougnan L, Lamiable D, et al. Troleandomycin-triazolam interaction in healthy volunteers pharmacokinetic and psychometric evaluation. EurJ Clin Pharmacol 1987 32 389-393. 

P450 enzymes may also be induced by substrate stabilization, eg, decreased degradation, as is the case with troleandomycin- or clotrimazole-mediated induction of CYP3A enzymes, the ethanol-mediated induction of CYP2E1, and the isosafrole-mediated induction of CYP1A2. 

Oleandomycin is a macrolide antibiotic produced by Streptomyces antibi-oticus. Oleandomycin and its triacetylated form, troleandomycin, are less effective than erythromycin against staphylococcal infections. They are usually administered orally or intravenously intramuscular administration is avoided because of the pain and tissue irritation it induces. Oleandomycin is also used in intramammary treatments and as a feed additive for growth promotion purposes. 

The toxicity of oleandomycin is quite low. Troleandomycin may cause hepatic disturbances and jaundice, liver function should be monitored in patients. 

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