Erythromycin salts

To the fiitered solution are added slowly and with stirring about 1,200 ml of anhydrous ether, to cause precipitation of erythromycin d-glucoheptonate and to keep In solution any excess of unreacted erythromycin. The precipitated erythromycin salt is removed by filtration through a sintered glass funnel, is washed with anhydrous ether and is dried in vacuo. Erythromycin d-glucoheptonate melts over a range of about 95° to 140°C. 

The pH-stability profile is a plot of reaction rate constant for drug degradation versus pH and may help to predict if some of the drug will decompose in the GI tract. The stability of erythromycin is pH-dependent. In acidic medium, erythromycin decomposition occurs rapidly, whereas at neutral or alkaline pH the drug is relatively stable. Consequently, erythromycin tablets are enteric coated to protect against acid degradation in the stomach. In addition, less soluble erythromycin salts that are more stable in the stomach have been prepared. 

Erythromycin (XX) is labile at pH values below pH 4, and hence is unstable in the stomach contents. Erythromycin stearate (the salt of the tertiary aliphatic amine and stearic acid), being less soluble, is not as susceptible to degradation. The salt dissociates in the intestine to yield the free base, which is absorbed. There are differences in the absorption behaviour of the erythromycin salts and differences in toxicity, which may be related to their aqueous solubilities. Erythromycin ethylsuccinate was originally developed for paediatric use because its low water solubility and relative tastelessness were suited to paediatric formulations. The soluble lactobionate is used in intravenous infusions. 

Ingestion is the most common route of both accidental and intentional exposures to erythromycin. Numerous erythromycin salt preparations are available in tablet, capsule, or liquid preparations for oral administration. Other available forms include intravenous, topical (acne), and ophthalmic preparations. 

PH Jones, EK Rowley, AL Weiss, DL Bishop, AHC Chun. Insoluble erythromycin salts. J Pharm Sci 58(3) 337, 1969. 

Spiramycin is a macrohde antibiotic. However, in contrast to other macrohde derivatives such as erythromycin salts, ototoxicity, neurosensorial disorders, and cardiac rhythm disorders do not appear to have been described after spiramycin. Reported adverse effects of spiramycin include G1 disorders, immune-allergic reactions, and liver injury (see also Figure 88). 

The acid-instabihty of erythromycin makes it susceptible to degradation in the stomach to intramolecular cyclization products lacking antimicrobial activity. Relatively water-insoluble, acid-stable salts, esters, and/or formulations have therefore been employed to protect erythromycin during passage through the stomach, to increase oral bioavakabihty, and to decrease the variabiUty of oral absorption. These various derivatives and formulations also mask the very bitter taste of macroHdes. 

Chemical Name Erythromycin glucoheptonic acid salt Common Name —... 

A complication here, however, is noted with those drugs that exhibit a limited chemical stability in either acidic or alkaline fluids. Since the rate and extent of degradation is directly dependent on the concentration of drug in solution, an attempt is often made to retard dissolution in the fluid where degradation is seen. There are preparations of various salts or esters of drugs (e.g., erythromycin) that do not dissolve in gastric fluid and thus are not degraded there but which dissolve in intestinal fluid prior to absorption. A wide variety of chemical derivatives are used for such purposes. 

The U. S. Dispensatory26 reports maximum serum levels of 0.2 ijg./ml. 1 hour after administration of a 250 mg. dose, 0.6 (ig./ml. 2 hours after a 500 mg. dose, and 1.2 ug./ml. 2 hours after a 1 g. dose. Higher blood levels are achieved on a multiple dosage schedule. Since it is acid labile, a resistant coating is used in tablet formulations to overcome the deleterious effect of gastric fluid on erythromycin base or the stearate salt is prepared which does not dissolve readily in the stomach. 

The incidence of side effects associated with erythromycin therapy is very low. Mild gastrointestinal upset with nausea, diarrhea, and abdominal pain are reported to occur more commonly when the propionate and es-tolate salts are used. Rashes are seen infrequently but may be a part of a general hypersensitivity reaction that includes fever and eosinophilia. Thrombophlebitis may follow intravenous administration, as may transient impairment of hearing. 

Cholestatic hepatitis may occur when drug therapy lasts longer than 10 days or repeated courses are prescribed. The hepatitis is characterized by fever, enlarged and tender liver, hyperbilirubinemia, dark urine, eosinophilia, elevated serum bilirubin, and elevated transaminase levels. Hepatitis has been associated with the estolate salt of erythromycin but not with other formulations. Although the hepatitis usually occurs 10 to 20 days after the initiation of therapy, it can occur within hours in a patient who has had such a reaction in the past. The hepatitis is believed to be the result of both a hepatotoxic effect and a hypersensitivity reaction this latter effect is reversible on withdrawal of the drug. Erythromycin and derivatives induce hepatic microsomal enzymes and interfere with the actions of various drugs, including theophylline and carbamazepine. 

The general structure of erythromycin is shown with the macrolide ring and the sugars desosamine and cladinose. It is poorly soluble in water (0.1%) but dissolves readily in organic solvents. Solutions are fairly stable at 4°C but lose activity rapidly at 20°C and at acid pH. Erythromycins are usually dispensed as various esters and salts. 

Secondary> hyperparathyroidism 30 mg PO daily Parathyroid carcinoma 30 mg PO bid titrate q2—4wk based on Ca PTH levels swallow whole take w/ food Caution [C, /—] w/ Szs Disp Tabs SE N/V/D, myalgia, dizziness, 4- Ca2+ Interactions T Effects W/ CYP3A4 inhibitors such as ketoconazole, itraconazole, erythromycin T effects OF drugs metabolized at CYP2D6 such as TCA, thioridazine, flecainide, vinblastine EMS Monitor ECG for signs of hypocalcemia (T QT interval) OD May cause severe hypocalcemia calcium salts can be given... 

In topical preparations, the base of erythromycin rather than a salt is used to facilitate penetration. Although the mechanism of action of topical erythromycin in inflammatory acne vulgaris is unknown, it is presumed to be due to its inhibitory effects on P acnes. One of the possible complications of topical therapy is the development of antibiotic-resistant strains of organisms, including staphylococci. If this occurs in association with a clinical infection, topical erythromycin should be discontinued and appropriate systemic antibiotic therapy started. Adverse local reactions... 

Heparin and its salts are incompatible with many drugs including alteplase, amikacin sulfate, amiodarone hydrochloride, ampicillin sodium, aprotinin, benzylpenicillin potassium or sodium, cephalothin sodium, ciprofloxacin lactate, cytarabine, dacarbazine, daunorubicin hydrochloride, diazepam, dobutamine hydrochloride, doxorubicin hydrochloride, droperidol, erythromycin lactobionate, gentamicin sulfate, haloperidol lactate, hyaluronidase, hydrocortisone sodium succinate, kanamycin sulfate, methicillin sodium, netilmicin sulfate, some opioid analgesics, oxytetracycline hydrochloride, some phenothiazines, polymyxin B sulfate, streptomycin sulfate, tetracycline hydrochloride, tobramycin sulfate, vancomycin hydrochloride, vinblastine sulfate, cisatracurium besylate, labetalol hydrochloride, nicardipine hydrochloride, cefmetazole, sodium ions, and fat emulsion.110 112... 

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