[Clinical experiments with erythromycin ethylsuccinate (erythromycin Abbott) in suppurative dental diseases in pedodontics].
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A sensitive and selective liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) method was developed for simultaneous identification and quantification of erythromycin ethylsuccinate and erythromycin in human plasma, which can be well applied to clinical study. The method was based on liquid-liquid extraction, followed by a LC procedure with an ODS C18 column, and mixture of acetonitrile and 1.67 mmol/l acetic acid as mobile phase. MS detection was performed using a single quadrupole mass spectrometer in positive selected ion monitoring (SIM) mode. The method was validated to be linear, precise and accurate. The lower limit of quantification of erythromycin ethylsuccinate and erythromycin were both 0.5 ng/ml. The proposed method enables the unambiguous identification and quantification of erythromycin ethylsuccinate and erythromycin for clinical drug monitoring.
Bioequivalence comparisons between erythromycin ethylsuccinate and an enteric-coated erythromycin base pellet product were made following multiple-dose, oral administration. Twenty-four volunteers participated in a ten-dose protocol (one dosage unit every six hours) using a complete crossover design. Plasma samples were assayed using a microbiological method specific for erythromycin base in the presence of the ester. Without correcting for the differences in doses administered, the amount of active erythromycin base absorbed from the enteric-coated pellet (250 mg base) was five to seven times that absorbed from the erythromycin ethylsuccinate product (400 mg base equivalent) at steady state. Erythromycin ethylsuccinate is not bioequivalent to an enteric-coated erythromycin base pellet product. The lower bioavailability of the ethylsuccinate may be due to instability in the acidic medium of the stomach.
The sulfonamides and erythromycin ethylsuccinate in combination oral suspensions were determined by high-performance liquid chromatography and automated turbidimetry, respectively. The chromatographic procedure was rapid, specific, and stability-indicating for sulfisoxazole acetyl and the trisulfapyrimidines using a reversed-phase system with UV detection at 254 nm. Erythromycin ethylsuccinate did not interfere with the sulfonamide analysis and these compounds were assayed with relative standard deviations (RDS) ranging from +/- 2.1 to +/- 3.1%. Erythromycin ethylsuccinate was determined as erythromycin with RSD values of +/- 1.3 or 3.5% without interference by the sulfonamides present.
In an open randomized multicenter study 190 culture-positive pediatric ambulatory pertussis patients were treated for 14 days with either erythromycin estolate (EST) (n = 93; 40 mg/kg/day divided in 2 doses) or erythromycin ethylsuccinate (ETH) (n = 97; 60 mg/kg/day divided in 3 doses). On day 14 Bordetella pertussis was recovered from cultures of 2 patients (2.2%) treated with EST and 1 patient (1.0%) treated with ETH. Despite the fact that 151 patients (79.4%) had reached the early paroxysmal stage at initiation of antimicrobial therapy, clinical improvement was seen in the majority (reduced frequency and severity of coughing: EST, 77.4 and 67.7%; ETH, 74.2 and 63.9%, respectively). Drug-related side effects were noted in 11 patients (11.8%) treated with EST and 16 patients (16.5%) treated with ETH (P greater than 0.05) and consisted mainly of minor gastrointestinal complaints. Erythromycin estolate in a lower dose administered only twice a day was equivalent to erythromycin ethylsuccinate in all aspects and proved to be adequate antimicrobial treatment for pertussis patients.
Serum concentrations of erythromycin were monitored in 11 healthy adult volunteers following single dose oral administration of erythromycin stearate, 1.5 g, and erythromycin ethylsuccinate 3.0 g. Peak serum concentrations occurred at 30 min to 2 h after the dose, usually at 1 h. Mean serum peak erythromycin concentrations (standard deviation) were 4.8 mg/l (+/- 2.0) following 1.5 g erythromycin stearate and 2.8 mg/l (+/- 1.4) after 3.0 g erythromycin ethylsuccinate. Both types of erythromycin frequently caused mild gastrointestinal side-effects but there were fewer side-effects associated with erythromycin ethylsuccinate. However, because of the increased serum erythromycin concentrations between 1 and 6 h after the dose of the stearate preparation compared to ethylsuccinate we recommend erythromycin stearate, 1.5 g, as the preferred loading dose, given 1 h before the dental procedure, for preventing endocarditis in susceptible patients allergic to penicillin.
The efficacy and tolerability of erythromycin ethylsuccinate, erythromycin base and erythromycin acistrate were studied in two separate randomized studies in 80 and 82 primary health care patients with upper respiratory tract infections. In Study I, the patients were given either ethylsuccinate 666 mg tid or base 500 mg qid for ten days. Possible side-effects, abdominal pain, nausea, diarrhoea and vomiting, were recorded daily by the patient. Study II followed the same design as Study I with the exception of the side-effect evaluation method. Patients were given in a randomized fashion ethylsuccinate 666 mg tid, or acistrate 400 mg qid. Side-effect evaluation was based on a 10-cm analogue visual scale to record abdominal pain, while nausea, vomiting and diarrhoea were recorded as daily frequencies. These studies indicated that erythromycin ethylsuccinate caused significantly less abdominal pain than the base form (chi 2-test), but there were no significant differences in tolerance between the ethylsuccinate and acistrate forms. Other tolerance parameters revealed no real differences. The clinical response was good with all erythromycin preparations at the doses used in this study.
The method described is capable of detecting less than 0.01 microgram/ml of erythromycin and/or erythromycin ethylsuccinate in serum. Recoveries of erythromycin and erythromycin ethylsuccinate, when added to the level of 0.6 microgram/ml, were 102 and 97% with relative standard deviations of 6.0 and 4.5%, respectively. Erythromycin ethylsuccinate in serum at 37 degrees was shown to degrade rapidly to erythromycin in a first-order rate. When stored at -20 degrees, however, only 10% of the erythromycin ethylsuccinate in serum was hydrolyzed even after storage for 36 days. The method was used to analyze erythromycin and erythromycin ethylsuccinate in sera from ten subjects administered with an oral dose of erythromycin ethylsuccinate. In addition to a small amount of anhydroerythromycin ethylsuccinate and 8,9-anhydro-6,9-hemiketal erythromycin ethylsuccinate, at least two other metabolites were detected in sera and one was tentatively identified as erythralosamine.
Relative bioavailability of erythromycin was determined after multiple-dose administration of erythromycin estolate in comparison to erythromycin ethylsuccinate both given as oral suspensions to twelve healthy volunteers. The daily erythromycin dose of erythromycin ethylsuccinate was 50% higher than the respective dose of erythromycin estolate; the dosage interval tau was 12 h for erythromycin estolate and 8 h for erythromycin ethylsuccinate. This scheme was planned in accordance to advices of the respective manufactures. Results of the study confirm the differences in extent of bioavailability of both erythromycin derivatives known from single-dose investigations. Furthermore, the experimental data show that a twice daily administration of 1000 mg erythromycin as erythromycin estolat resulted in sufficiently high plasma concentration of the active compound.
Two patients experienced hepatotoxicity associated with erythromycin estolate (Ilosone) usage, followed 13 and 15 years later by an hepatotoxic reaction with administration of erythromycin ethylsuccinate (E.E.S.). These cases provide further evidence for erythromycin ethylsuccinate-associated hepatotoxicity and demonstrate erythromycin cross-sensitivity after previous erythromycin estolate liver injury. Hepatotoxicity to both sensitivity after previous erythromycin estolate liver injury. Hepatotoxicity to both estolate and ethylsuccinate preparations of erythromycin stimulates speculation regarding the potentially hepatotoxic moiety of the erythromycin molecule. Furthermore, these cases suggest that all erythromycin preparations should be avoided or used only with careful monitoring in patients with previous erythromycin-associated liver injury.
Although erythromycin estolate has been fully assessed for pertussis treatment, the evaluation of erythromycin ethylsuccinate and stearate, the main erythromycin preparations used in Japan and the US, is inadequate. We evaluated these preparations to establish an appropriate treatment for pertussis according to age. Sixty-six patients with culture-confirmed pertussis were treated with erythromycin administered at a dosage of 40-50 mg/kg/day (maximum, 1.2 g/day). Negative culture was obtained in 39% (15/38) of patients aged 0-2 years within one week and in 71% (27/38) within two weeks, in 78% (7/9) of those aged 3-15 years within one week and in 100% (9/9) within two weeks. All 12 adult patients had a negative culture within one week. The efficacy of erythromycin for the eradication of B. pertussis was significantly lower in children aged 0-2 years than in older children. In conclusion, it is desirable to administer erythromycin for three weeks to children aged 0-2 years, two weeks to those aged 3-15 years and one week to adults.
Roxithromycin is a novel oxime ether derivative of erythromycin. Previous studies have demonstrated similar in-vitro activity for roxithromycin and erythromycin. Roxithromycin has improved pharmacokinetic properties and may be a useful alternative agent for infections where erythromycin is indicated. We compared the efficacy and toxicity of roxithromycin and erythromycin ethylsuccinate in the treatment of streptococcal pharyngitis in adults. We also assessed compliance with treatment between the two agents. Roxithromycin and erythromycin ethylsuccinate were equally effective in resolving the symptoms and signs of pharyngitis. Erythromycin ethylsuccinate was superior to roxithromycin in achieving microbiological cure (90% vs. 33%, respectively). No differences were observed in toxicity or compliance with treatment between the two agents. Based on this prespective clinical trial, roxithromycin is not considered to be an acceptable alternative agent for acute streptococcal pharyngitis in adults.
An investigator blind trial was performed comparing bismuth salicylate, erythromycin ethylsuccinate, and placebo in the treatment of Campylobacter pyloridis associated gastritis in patients without peptic ulceration. Fifty patients fulfilled the study criteria. There was a strong correlation between the presence of C pyloridis and histologically confirmed gastritis. Clearance of organisms led to improvement of the gastritis. C pyloridis was cleared from 15 patients; of these, 13 had gastritis initially, which resolved in 12. Conversely, gastritis resolved in only four of 32 patients not cleared of organisms (p less than 0.0001). There was significantly greater improvement in endoscopic appearances in the patients cleared of C pyloridis compared with those whose infection persisted (p less than 0.001). In the three treatment groups organisms were cleared from 14 of 18 patients receiving the locally active bismuth salicylate, only one of 15 patients receiving erythromycin ethylsuccinate, and none of 17 patients taking placebo. These findings suggest that the ideal antimicrobial for the successful eradication of C pyloridis associated gastritis should be locally active, stable at low pH, and should penetrate gastric mucus. The resolution of gastritis and improvement in endoscopic appearances associated with clearance of C pyloridis support the view that these organisms may play a part in this condition.
In a double blind, randomised investigation in 193 hospitalized patients, with low respiratory infections, roxithromycin (150 mg bd) and erythromycin ethylsuccinate (1 g bd) were compared. Assessment of safety was made in 183 patients and clinical response in 155 patients. The mean duration of treatment was 11 days in both groups. Clinical effectiveness was 82% (67/82) for roxithromycin and 77% (56/73) for erythromycin ethylsuccinate. Roxithromycin appears to have a good effectiveness and to be effective as erythromycin ethylsuccinate. The safety profile is satisfactory in both groups.
Macrolides are potential gastrokinetic agents. The purpose of this study was to assess the effect of a single oral dose of two erythromycin formulations on gastric emptying of the solid and liquid phases in twelve healthy volunteers and to seek a correlation between pharmacokinetic parameters and changes in gastric emptying. The gastric emptying times of liquids and solids were measured simultaneously by means of a scintigraphic technique after a single oral administration of amorphous erythromycin ethylsuccinate (500 mg), crystalline erythromycin ethylsuccinate (1000 mg) or a placebo, in a double-blind crossover study in three separate weeks. Blood samples were obtained for erythromycin assay. The two oral formulations induced a similar acceleration of gastric emptying. When compared to the placebo, both erythromycin preparations significantly shortened the gastric transit time of solids and liquids (respectively 30% and 20% on average, p < 0.01). The incidence of gastrointestinal side-effects was similar with the two erythromycin forms and the placebo. No correlation was found between the peak serum erythromycin concentrations and the solid or liquid gastric half-lives. With the amorphous formulation, the area under the plasma time-concentration curves was small and solid and liquid gastric emptying were strongly accelerated, pointing to a direct effect on the gastrointestinal smooth muscle.
A total of 619 patients with acute upper or lower respiratory tract infection were randomised to receive either erythromycin ethylsuccinate tablets at a dose of 1 g twice daily, or ciprofloxacin tablets 500 mg twice daily in a single-blind, multicentre study. The efficacy of each antibacterial was similar, with close to 90% of patients on each treatment being reported as either cured or improved. Gastrointestinal symptoms were the most commonly reported side-effects, being similar in overall incidence for both agents. Nausea, vomiting, dizziness and headache occurred more frequently in the ciprofloxacin group, while abdominal pain and diarrhoea occurred more frequently in the erythromycin ethylsuccinate group. In each group, the number of patients failing to complete treatment was similar and the main reasons cited for discontinuation were gastrointestinal symptoms. This study indicates that both erythromycin ethylsuccinate and ciprofloxacin are well tolerated and are equally effective for routine empirical treatment of acute respiratory tract infections.
Universal quantitative models using NIR reflectance spectroscopy were developed for the analysis of API contents (active pharmaceutical ingredient) in roxithromycin and erythromycin ethylsuccinate tablets from different manufacturers in China. The two quantitative models were built from 78 batches of roxithromycin samples from 18 different manufacturers with the API content range from 19.5% to 73.9%, and 66 batches erythromycin ethylsuccinate tablets from 36 manufacturers with the API content range from 28.1% to 70.9%. Three different spectrometers were used for model construction in order to have robust and universal models. The root mean square errors of cross validation (RMSECV) and the root mean square errors of prediction (RMSEP) of the model for roxithromycin tablets were 1.84% and 1.45%, respectively. The values of RMSECV and RMSEP of the model for erythromycin ethylsuccinate tablets were 2.31% and 2.16%, respectively. Based on the ICH guidelines and characteristics of NIR spectroscopy, the quantitative models were then evaluated in terms of specificity, linearity, accuracy, precision, robustness and model transferability. Our study has shown that it is feasible to build a universal quantitative model for quick analysis of pharmaceutical products from different manufacturers. Therefore, the NIR method could be used as an effective method for quick, non-destructive inspection of medicines in the distribution channels or open market.