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At least 19 recordsLinked to original sources
PubMed1988

Concentrations of erythromycin, 2'-acetyl erythromycin, and their anhydro forms in plasma and tonsillar tissue after repeated dosage of erythromycin stearate and erythromycin acistrate.

The concentrations of erythromycin, 2'-acetylerythromycin (2'-AE) and their anhydro forms in plasma and tonsillar tissue were analyzed after a 3-day repeated-dosage regimen of erythromycin stearate (ES; 500 mg twice a day [b.i.d]) and erythromycin acistrate (EA), a new erythromycin prodrug, at two doses (400 and 500 mg b.i.d.). The tonsils of 40 patients were removed at 112 to 329 min after intake of the last dose. Blood samples were collected at the time of tonsillectomy and at 0, 2, and 6 h after the last dose. At all time points, EA produced severalfold more total antibiotic (erythromycin + 2'-AE) concentrations in plasma compared with ES. There were two nonabsorbers in the ES group, but none in the two EA groups. The mean total antibiotic levels in tonsillar tissue after EA treatment exceeded the levels after treatment with ES by a factor of 3 (for EA at 400 mg b.i.d.) and 4.5 (for EA at 500 mg b.i.d.). The ratios of erythromycin concentration in tonsil to that in plasma at the time of tissue removal were quite similar for all groups (means, 0.51 to 0.54). In the EA groups, 2 of 26 (8%) patients had no measurable erythromycin in the tonsillar tissue samples, whereas in the ES group, 3 of 14 (21%) patients had no measurable erythromycin in the same tissue. The degree of hydrolysis of 2'-AE to erythromycin was about 25% in plasma at the time of tonsillectomy for both EA groups and about 40% in tonsillar tissue. There were negligible amounts of anhydro forms in plasma after EA administration, whereas in the ES group, anhydroerythromycin levels were, from time to time, even higher than erythromycin levels. Very high levels of anhydro forms were detected in tonsillar tissue after ES treatment, whereas only low levels were found after EA administration.

Child↗
PubMed1988

Fate of single oral doses of erythromycin acistrate, erythromycin stearate and pelleted erythromycin base analysed by mass-spectrometry in plasma of healthy human volunteers.

The kinetics of erythromycin acistrate (EA). a new ester prodrug of erythromycin, were studied in three comparative, randomized, cross-over studies in 29 healthy volunteers. A new mass-spectrometric method was used to assay separately erythromycin, 2'-acetyl erythromycin and their anhydro (spiroketal) forms. In Part I, the total antibiotic concentration was higher after EA than after erythromycin stearate (ES; 1.8-fold) and enterocoated pellets of erythromycin base (EB, enterocapsules; 1.4-fold). In plasma, however, only about one third of 2'-acetyl erythromycin was hydrolysed to active erythromycin. Moreover, after unprotected EA tablets, a considerable proportion of erythromycin and 2'-acetyl erythromycin was inactivated by gastric acid as reflected by high concentrations of respective anhydro (spiroketal) forms. In Part II, the unprotected (regular tablets) and acid-protected tablets (dissolution starts at pH 4.5) were compared. The protected tablet, albeit not an enterotablet, was not destroyed by gastric acid. Its absorption was slightly delayed but the bioavailability was good. In this study, the absorption of total antibiotic was 2.8-fold (unprotected tablet) and 3.9-fold (protected tablet) that after enterocapsules. In Part III, the bioavailabilities of 200 and 400 mg tablets (both acid-protected) were equal.

Administration, Oral↗
PubMed1993

Erythromycin and 2'-acetyl erythromycin concentrations in plasma and pelvic tissues after repeated doses of erythromycin acistrate.

The concentrations of erythromycin (E) and 2'-acetyl erythromycin (2'-AE) in female pelvic organs, i.e. endometrium, myometrium, ovary and Fallopian tube, as well as in plasma, were determined after oral dosing of erythromycin acistrate (EA, CAS 96128-89-1), a erythromycin prodrug. Ten patients undergoing selective gynecological operation were given three doses of EA (400 mg) at 8-h intervals immediately before the operation. Tissue samples were taken 75-205 min after the intake of the last dose. Blood samples were collected immediately prior to and up to 8 h after the intake of the last dose. High total antibiotic (erythromycin + 2'-acetyl erythromycin) concentration in plasma were measured throughout the dose interval after the last dose. The concentrations of E in plasma were over the MICs for most of the erythromycin-sensitive bacteria (0.5 micrograms/ml) in 7 out of 10 patients (mean 0.66 micrograms/ml) at the end of the third dose interval. The drug concentrations in tissues were lower than in plasma (due to short treatment time of totally 24 h). The mean percentage of penetration (tissue/plasma ratios) for erythromycin ranged from 63 to 95% in various pelvic tissues. However, rather extensive interindividual variation was observed. The degree of hydrolysis of 2'-acetyl erythromycin to erythromycin was 29-39% in plasma and 42-73% in tissue samples. There were negligible amounts of inactive anhydro forms in plasma after EA and their concentrations in tissue samples were low, as well.

Biotransformation↗
PubMed1992

Studies on the intravenous pharmacokinetics in rabbit and in vitro protein binding of two new salts of erythromycin: erythromycin maltobionate and erythromycin fumarate.

Pharmacokinetics in rabbits following intravenous administration and in vitro protein binding were studied for two new salts of erythromycin (erythromycin maltobionate and erythromycin fumarate). Serum erythromycin levels following intravenous injection were described by two compartment model kinetics, and values for the distribution volume of the central compartment, the peripheral compartment and overall distribution volume were calculated. The elimination half-lives of erythromycins in serum were 83 min, 168 min, and 103 min for erythromycin maltobionate, erythromycin fumarate, and erythromycin lactobionate (reference standard), respectively. The erythromycin salts were highly (c. 90 per cent) protein bound, but the binding was found to be reversible. Differences in the pharmacokinetic parameters after administration of equivalent doses of the salts, indicate possible variation in efficacies of different salts.

Animals↗
PubMed1991

Penetration of erythromycin into periapical lesions after repeated doses of erythromycin acistrate and erythromycin stearate: a pilot study.

In 26 patients who had undergone apicectomy and extirpation of granulomas (n = 9) or radicular cysts (n = 17), concentrations of erythromycin, 2'-acetyl erythromycin, and their anhydro forms were determined with a novel chemical method in plasma and periapical lesions after at least 2 days of treatment with erythromycin acistrate (EA) (400 mg three times daily, n = 11) or erythromycin stearate (ES) (500 mg three times daily, n = 15). Oral surgery was performed 2 1/2 to 3 hours after the last dose. Blood samples were collected at the time of operation, and immediately before antibiotic treatment, and 1, 2, and 6 hours after treatment. At all time points EA produced at least twice the total antibiotic (2'-acetyl erythromycin plus erythromycin) concentrations in plasma as ES. Erythromycin levels in plasma were at least as high after EA treatment as after ES. In periapical lesions erythromycin concentration after EA was three times higher (1.34 +/- 0.28 micrograms/gm) than after ES treatment (0.40 +/- 0.17 micrograms/gm). Although the total drug concentration in periapical lesions was about the same after EA (2.64 micrograms/ml) and ES (3.41 micrograms/ml), most of the drug recovered after ES was antimicrobially inactive anhydroerythromycin (3.01 micrograms/gm). The concentration of anhydroerythromycin in plasma was approximately the same as that of erythromycin after ES throughout the dose interval. After EA treatment both plasma and the periapical lesion samples contained hardly detectable amounts of anhydroerythromycin. Hence EA has a good bioavailability essential for treatment and prophylaxis of bacterial infections in dentistry.

Adult↗
PubMed1992

The effect of zinc and erythromycin on the growth of erythromycin-resistant and erythromycin-sensitive isolates of Propionibacterium acnes: an in-vitro study.

The effect of zinc and erythromycin on cultures inoculated with mixtures of different ratios of erythromycin sensitive (ES) and resistant (ER) Propionibacterium acnes cells was studied in vitro. Propionibacterium acnes ES outgrew P. acnes ER in the absence of erythromycin and zinc. At low levels of erythromycin ES outgrew ER, whilst the addition of 600 pg/ml zinc further reduced the growth of ER compared to ES. Growth of ER and ES were similar at levels of erythromycin near the minimum inhibitory concentration (MIC) of ES cells. Concentrations above the MIC for ES cells inhibited ES but not ER cells. At the higher concentrations of erythromycin, the addition of 96 ng/ml zinc delayed the growth of ER cells, whilst the addition of 300 micrograms/ml zinc prevented the growth of ER cells. The combination of erythromycin and zinc, at appropriate concentrations, inhibits both ES and ER.

Bacteriological Techniques↗
PubMed1989

Efficacy of erythromycin acistrate (2'-acetyl erythromycin stearate) and erythromycin stearate in experimental infections in mice.

The efficacy of erythromycin stearate (ES) and its 2'-acetyl ester (erythromycin acistrate, EA) was compared in eight experimental infections in mice of both sexes. In two studies the mice were made leukopenic by whole-body irradiation. Four absorption studies were also performed in parallel. In Streptococcus pneumoniae peritonitis, the protective dose 50% (PD50) value of EA and ES, given s.c., did not differ from each other. The bioavailability of EA was slightly inferior to that of ES. In three other peritonitis studies (2 Staphylococci and 1 Streptococcus), where the treatments were given s.c., EA seemed to lag behind ES in efficacy. The parallel absorption experiment showed, however, that, as compared to ES, only about one-half of EA was released from the s.c. injection site to the blood. The adjusted PD50 values of both erythromycins were about the same, with one exception. When the treatments were given i.p. both erythromycins were equally effective, and the difference in bioavailability was minor. On the contrary, the efficacy of 2'-ethylsuccinyl erythromycin was only about one-tenth that of the other erythromycins as was also the bioavailability. Oral treatment gave similar therapeutic results with EA and ES, with similar bioavailabilities, too. In the muscle abscess model, single s.c. injections of EA and ES were equally effective in reducing the growth of Staphylococcus aureus. These results suggest that there is no great difference in the in vivo antibacterial performance of ES and its 2'-acetyl ester, although the absorption problems complicate the interpretation. Hence EA performs better than expected if only the hydrolyzed drug were useful.

Animals↗
PubMed1980

Comparative bioavailability evaluation of erythromycin base and its salts and esters. I. Erythromycin estolate capsules versus enteric-coated erythromycin base tablets.

A randomized crossover study in 16 healthy volunteers given multiple doses of erythromycin base enteric-coated tablets or erythromycin estolate capsules revealed essentially no difference in the resultant plasma concentration of bioactive erythromycin. This similarity in bioactivity persisted despite the fact that total eryghromycin levels (bioactive erythromycin base plus bioinactive erythromycin propionate) were at least three times higher after administration of the estolate than after administration of the base.

Adult↗
PubMed1992

Comparison of erythromycin estolate and erythromycin ethylsuccinate for treatment of pertussis. The Erythromycin Study Group.

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.

Child↗
PubMed1981

Comparison of serum erythromycin concentration following administration of 100 mg erythromycin ethyl succinate intramuscularly and 500 mg erythromycin stearate orally.

Serum erythromycin concentrations were estimated following administration of 100 mg erythromycin ethyl succinate intramuscularly and 500 mg erythromycin stearate orally. The subjects (30 healthy students) were randomly divided into two groups and each subject received a single dose of the alternate form of the drug after a 4-week interval. Blood samples were obtained at 0.5, 1, 1.5, 2, 3 and 4 h after administration by separate venepuncture. All 30 subjects recorded serum levels above 0.2 microgram/ml following administration of the intramuscular form of the drug. Following administration of the oral form of the drug, five subjects failed to record serum levels above 0.2 microgram/ml by the 2-h sampling time and three failed to do so by the 4th hour. It is concluded from the results that, despite the high serum levels recorded with the oral form when taken with food, the intramuscular route gives a greater assurance of consistent absorption into the blood stream. This result suggests that the use of the oral form of the drug as a prophylactic antibiotic in patients receiving dental treatment remains in doubt.

Administration, Oral↗
PubMed2003

A novel erythromycin, 6-desmethyl erythromycin D, made by substituting an acyltransferase domain of the erythromycin polyketide synthase.

The acyltransferase (AT) domain in module 4 of the erythromycin polyketide synthase (PKS) was substituted with an AT domain from the rapamycin PKS module 2 in order to alter the substrate specificity from methylmalonyl-CoA to malonyl-CoA. The resulting strain produced 6-desmethyl erythromycin D as the predominant product. This AT domain swap completes the library of malonyl-CoA AT swaps on the erythromycin PKS and reinforces PKS engineering as a robust and generic tool.

Acyltransferases↗
PubMed2000

Pharmacokinetics of erythromycin estolate and erythromycin phosphate after intragastric administration to healthy foals.

OBJECTIVE: To determine pharmacokinetics and plasma concentrations of erythromycin and related compounds after intragastric administration of erythromycin phosphate and erythromycin estolate to healthy foals. ANIMALS: 11 healthy 2- to 6-month-old foals. PROCEDURE: Food was withheld from foals overnight before intragastric administration of erythromycin estolate (25 mg/kg of body weight; n = 8) and erythromycin phosphate (25 mg/kg; 7). Four foals received both drugs with 2 weeks between treatments. Plasma erythromycin concentrations were determined at various times after drug administration by use of high-performance liquid chromatography. Maximum plasma peak concentrations, time to maximum concentrations, area under plasma concentration versus time curves, half-life of elimination, and mean residence times were determined from concentration versus time curves. RESULTS: Maximum peak concentration of erythromycin A after administration of erythromycin phosphate was significantly greater than after administration of erythromycin estolate (2.9 +/- 1.1 microg/ml vs 1.0 +/- 0.82 microg/ml). Time to maximum concentration was shorter after administration of erythromycin phosphate than after erythromycin estolate (0.71 +/- 0.29 hours vs 1.7 +/- 1.2 hours). Concentrations of anhydroerythromycin A were significantly less 1 and 3 hours after administration of erythromycin estolate than after administration of erythromycin phosphate. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma concentrations of erythromycin A remained > 0.25 microg/ml (reported minimum inhibitory concentration for Rhodococcus equi) for at least 4 hours after intragastric administration of erythromycin phosphate or erythromycin estolate, suggesting that the recommended dosage for either formulation (25 mg/kg, q 6 h) should be adequate for treatment of R equi infections in foals.

Animals↗
PubMed1996

The effects of acne treatment with a combination of benzoyl peroxide and erythromycin on skin carriage of erythromycin-resistant propionibacteria.

Concomitant application of 5% w/w benzoyl peroxide and 3% w/w erythromycin has previously been shown to prevent the overgrowth, on the skin of acne patients, of erythromycin-resistant coagulase-negative staphylococci, which occurs when the antibiotic is used alone. Two in vivo studies were carried out to assess the ability of the same therapeutic combination to inhibit the growth of pre-existing erythromycin-resistant propionibacteria and to prevent the selection of resistant strains during treatment. A double-blind clinical trial in 37 patients with mild to moderate acne vulgaris showed that the combination brought about a > 3 log10 c.f.u. reduction in total propionibacterial numbers/cm2 after 6 weeks therapy (P < 0.001, Wilcoxon's matched pairs) and also significantly reduced the number of erythromycin-resistant propionibacteria (P < 0.05). In contrast, erythromycin alone reduced the total propionibacterial count by < 1.5 log10 c.f.u./cm2 after 6 weeks (P < 0.05) and did not affect the number of erythromycin-resistant strains. The combined formulation was significantly more effective at reducing total propionibacterial numbers at 6 (P < 0.01, Mann-Whitney) and 12 weeks (P < 0.05) than erythromycin alone, although, after 12 weeks, the anti-propionibacterial efficacy of both preparations was less marked. Five patients on combination therapy, and five treated with erythromycin alone, acquired erythromycin-resistant strains de novo at week 6 or week 12. In an open study in 21 acne patients, who each carried > 10(3) c.f.u. erythromycin-resistant propionibacteria/cm2 skin pretreatment, the combination of erythromycin and benzoyl peroxide reduced the total propionibacterial count by > 2.5 log10 and the number of erythromycin-resistant strains by a similar amount (P < 0.001, Wilcoxon). This was accompanied by highly significant reductions in acne grade and lesion counts (P < 0.001). These data suggest that the combination of 5% w/w benzoyl peroxide and 3% w/w erythromycin has greater in vivo anti-propionibacterial activity than 3% w/w erythromycin alone, and brings about significant clinical improvement in acne patients with high numbers of erythromycin-resistant propionibacterial strains pretreatment.

Acne Vulgaris↗
PubMed1988

Antibiotic concentration in suction skin blister fluid and saliva after repeated dosage of erythromycin acistrate and erythromycin base.

The drug concentration in plasma, suction skin blister fluid (SBF), urine and saliva after repeated dosage of either erythromycin acistrate (EA) or enterocoated pellets of erythromycin base (EB) was studied in young healthy volunteers with a cross-over design in two separate studies. In Study I, the total drug concentration (erythromycin + 2'-acetyl erythromycin) after EA (400 mg tid) was slightly higher than the erythromycin concentration after EB (500 mg tid). The concentration of erythromycin after EA was about half of that after EB. In SBF the total antibiotic concentration after EA and erythromycin concentration after EB were 49 and 46% of the corresponding plasma concentrations, respectively. The degree of hydrolysis of 2'-acetyl erythromycin was higher in SBF (44%) than in plasma (39%). An equal proportion (7.3-7.5%) of the dose was excreted in urine after administration of both drugs. The degree of hydrolysis of 2'-acetyl erythromycin in urine was 58%. In Study II, the plasma/saliva concentration ratio ranged from 0.11 to 0.17 after EA 400 mg tid, 0.12 to 0.20 after EA 500 mg tid and 0.17 to 0.22 after EB 500 mg tid. The degree of hydrolysis of 2'-acetyl erythromycin was considerably higher in saliva (61-78%) than in plasma (27-41%). In plasma, the percentage of hydrolysis of 2'-acetyl erythromycin was inversely correlated with the concentration of acid-alpha 1-glycoprotein. The penetration of 2'-acetyl erythromycin and erythromycin into the extravascular space as evaluated from SBF and saliva levels was equal, and adequate concentrations of erythromycin were obtained for the treatment of bacterial infections.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

[Comparison of the bioavailabilities of erythromycin estolate and erythromycin ethylsuccinate dry suspension preparations in steady state].

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.

Adult↗
PubMed1978

Fluorimetric determination of erythromycin and erythromycin ethylsuccinate in serum by a high-performance liquid chromatographic post-column, on-stream derivatization and extraction method.

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.

Chromatography, High Pressure Liquid↗
PubMed1974

Effect of erythromycin analogues on binding of [14C]erythromycin to Escherichia coli ribosomes.

The relative ability of 44 erythromycin analogues to bind to ribosomes was determined by their effect on [(14)C]erythromycin binding to Escherichia coli ribosomes. The association and dissociation constants of each of these erythromycin derivatives were determined as well as their interaction coefficient for their binding to ribosomes. Substitutions were made on various portions of the erythromycin molecule with retention of substantial activity as measured by inhibition of [(14)C]erythromycin binding to ribosomes. Since the effect of erythromycin analogues on [(14)C]erythromycin binding to ribosomes provides a relatively sensitive assay for these compounds, erythromycin analogues with relatively little affinity for ribosomes could be detected. Compounds with association constants of 10(4) M(-1) were detectable; the association constant for erythromycin binding to ribosomes was approximately 10(8) M(-1). Thus, compounds with 0.0001 the association constant of erythromycin were detectable. This assay could be used alone or in conjunction with microbiological assays for primary screening of active analogues or other compounds which interfere with [(14)C]erythromycin binding to ribosomes. It permits an estimate of the general activity of compounds rapidly and directly. Variables such as metabolic modifications of the compounds and permeability are excluded. The present assay reflects the ability of the compounds to interact directly with their target organelle and may serve as a useful adjunct in developing new compounds.

Carbon Radioisotopes↗