Erythromycin Ethanol

Clinically important, potentially hazardous interactions with alcohol, cimetidine, CNS depressant, erythromycin, ethanol, ketoconazole, nefazodone, nelfinavir, olanzapine, rifampin, ritonavir, tricyclic antidepressants... 

Other drugs that inhibit hepatic cytochromes P450 include chloramphenicol, cimeti-dine, clarithromycin, disulfiram, erythromycin, ethanol, grapefruit juice (contains fu-ranocoumarins), ethinyl estradiol, fluconazole, isoniazid, itraconazole, MAO inhibitors, phenylbutazone, and secobarbital. 

A solution of 10 grams of d-glucoheptonic acid lactone in 50 ml of distilled water is warmed on a steam bath for about 2 hours to hydrolyze the lactone to the acid. The mixture is cooled and 100 ml of 95% ethanol are added. To the solution of glucoheptonic acid are added about 37 grams of erythromycin and the volume of the reaction mixture is brought to 200 ml by the addition of 95% ethanol. The reaction mixture is stirred for about 2 hours and is filtered through a porcelain filter candle of porosity 02. To provide a steriie product, aseptic technique is used throughout the remainder of the procedure. 

Antibiotics may be classified by chemical structure. Erythromycin, chloramphenicol, ampicillin, cefpodoxime proxetil, and doxycycline hydrochloride are antibiotics whose primary structures differ from each other (Fig. 19). Figure 20 shows potential oscillation across the octanol membrane in the presence of erythromycin at various concentrations [23]. Due to the low solubility of antibiotics in water, 1% ethanol was added to phase wl in all cases. Antibiotics were noted to shift iiB,sDS lo more positive values. Other potentials were virtually unaffected by the antibiotics. On oscillatory and induction periods, there were antibiotic effects but reproducibility was poor. Detailed study was then made of iiB,sDS- Figure 21 (a)-(d) shows potential oscillation in the presence of chloramphenicol, ampicillin, cefpodoxime proxetil, and doxycycline hydrochloride [21,23]. Fb.sds differed according to the antibiotic in phase wl and shifted to more positive values with concentration. No clear relationship between activity and oscillation mode due to complexity of the antibacterium mechanism could be discovered but at least it was shown possible to recognize or determine antibiotics based on potential oscillation measurement. 

Our laboratories10 have developed a system separating erythromycin estolate, erythromycin base, and anhydroerythromycin on a silica gel 60 F-254 plate utilizing ethanol, methanol, triethylamine, 170 30 1. Visualization is made by spraying with 0.15% xanthydrol and 7.5% acetic acid in water. Table V summarizes the Rf s. 

Erythromycin, a macrolide antibiotic, lacks a significant chromophore. Detection sensitivity was enhanced by using a wavelength of 200 nm and selecting an injection solvent of lower conductivity than the BGE. In order to facilitate the separation of erythromycin and its related substances, 35% (v/v) ethanol was incorporated into a 150 mM phosphate buffer pH 7.5. Resolution of all of the compounds was achieved in approximately 45 min. The method was employed as an assay method for erythromycin and for impurity determination. Peptide antibiotics, such as colistin and polymyxin, are mixtures of many closely related compounds. A validated CZE method for impurity analysis of polymyxin B was described, employing 130 mM triethanolamine-phosphate buffer at pH 2.5 to reduce the adsorption of analyte onto the capillary wall. Methyl-/l-cyclodextrin (M-/1-CD) and 2-propanol were found to be necessary for selectivity enhancement. Using similar buffer additives, the same group developed and validated a method for colistin analysis. ... 

FIGURE 10 Isocratic CEC of erythromycin A and its impurities. Cationic column 30cm (effective length 20 cm) x 50 pm ID mobile phase 25% (v/v) acetonitrile and 25% (v/v) ethanol in 30mM phosphate buffer, pH 8.0 applied voltage — l5kV detection, 206 nm. Sample (I) N-demethylerythromycin A, (2) erythromycin C, (3) erythromycin A, (4) erythromycin B, (5) erythromycin enol ether. Mobility of EOF measured with DMSO, peof = 3-33 x 10 °m /sV. (Reprinted from reference 321, with permission.)... 

The taxanes are practically insoluble in water and solubility is limited to mixtures of ethanol with poly-ethoxylated castor oil. They are generally administered in 3-24 hour infusions. The taxanes are for 90-95% plasma protein bound and primarily metabolized by P450 enzymes in the liver. Less than 10% is excreted in the urine as parent compounds. The elimination half-life of docetaxel is approximately 10 hours while that of paclitaxel has been vary-ingly reported between 5 and 50 hours. Inhibitors of the cytochrome P450 isoenzyme Cyp3A4, like keto-conazole and erythromycine, are contraindicated. 

Erythromycin and erythromycin estolate can be separated and quantitated by thin layer chromatography.Samples or standards should approximate 50 meg erythromycin estolate and 5-10 meg erythromycin base when spotted on silica gel G-25 plates. Approximately 120 ml of the developing solvent (methanol A.R.) is placed into the developing tank and allowed to equilibrate. The plate is developed until the solvent is approximately 15 cm from the origin The plate is removed and allowed to air dry. Antibiotic spots are visualized by spraying the plate with a fresh mixture of 95 ethanol/anis-aldehyde/conc. sulfuric acid, 90 5 5(v/v) followed by heating of the plate at 110 C for 10 minutes. The Rf values of erythromycin estolate and erythromycin base are approximately 0.7 and 0.35 respectively. 

Pancreatic dysfunction, heralded by large increases in serum amylase and lipase, is associated with the use of several reverse-transcriptase inhibitors (RTIs). Didanosine appears to be the worst offender, and pancreatitis is the most characteristic adverse effect of this particular NRTI. Conditions enhancing susceptibility to drug-induced pancreatic dysfunction include hypertriglyceridemia, hypercalcemia, and history of excessive ethanol use. Liver dysfunction including hepatitis may occur with the antitu-bercular drugs, isoniazid, and pyrazinamide. Cholestasis is associated with the estolate form of erythromycin. 

FIG. 28 Correspondence of the lower potential of the first pulse,. EB SDS, in the presence of antibiotics to bitterness scores of aqueous solution containing antibiotics and 1% ethanol in phase wl (O) ampicillin, ( ) erythromycin, (A) chloramphenicol, and (V) cefpodoxime proxetil. Phases w2 and o the same as in Fig. 8. (Ref. 23.)... 

Amorphous base, slightly sol in water. — 80" (methanol). uv max (ethanol) 231 am. So) in most organic solvents. Active on gram-positive bacteria and rickcttsiae. Cross resistance between microorganisms resistant to erythromycin and carbomycin. LDM in rats (mg/kg) 9400 orally 1000 s-c- 170 i.v. (Sous). 

Erythromycin ethyl succinate is a mixed double ester pro-drug in which one carboxyl of succinic acid esterifies the C-2 hydroxyl of erythromycin and the other ethanol (Fig. 38.28). This pro-drug frequently is used in an oral suspension for pediatric use largely to mask the bitter taste of the drug. Film-coated tablets also are used to deal with this. Some cholestatic jaundice is associated with the use of EES. 

Nordmann R, Ribiere C, Rouach H (1992) Implication of free radical mechanisms in ethanol-induced cellular injury. Free Radical Biol Med 112 219-240 Oh KW, Qian T, Brenner DA, Lemasters JJ (2003) Salicylate enhances necrosis and apoptosis mediated by the mitochondrial permeability transition. Toxicol Sci 73 44—52 Okanoue T, Sakamoto S, Itoh Y, Minami M, Yasui K, Sakamoto M, Nishioji K, Katagishi T, Nakagawa Y, Tada H, Sawa Y, Mizuno M, Kagawa K, Kashima K (1996) Side effects of high-dose interferon therapy for chronic hepatitis C. J Hepatol 25 283-291 Oleinick NL, Corcoran JW (1969) Two types of binding of erythromycin to ribosomes Ifom antibiotic-sensitive and resistant Saci/te suhtilis 168. J Biol Chem 244 727-735 Oyadomari S, Mori M (2004) Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Diff 11 381-389... 

A large number of solvates have been reported, especially for steroids and antibiotics. It has been observed that cortisone acetate and dexamethasone acetate can be crystallized as 10 different solvates. Dirithromycin, a semisynthetic macrolide antibiotic, crystallizes in two anhydrous polymorphic forms and in at least nine stoichiometric solvate forms. Six of the known solvates are isomorphic, having nearly identical x-ray powder diffraction patterns [76]. In addition to the anhydrate and dihydrate, erythromycin also forms solvates with acetone, chloroform, ethanol, n-butanol, and/-propanol [77]. 

---