Comparison of the effect of azithromycin versus erythromycin on antroduodenal pressure profiles of patients with chronic functional gastrointestinal pain and gastroparesis.

BACKGROUND: Current pharmacologic treatments for gastroparesis have been disappointing due to the limited options available. Erythromycin ethylsuccinate is a potent prokinetic agent that stimulates gastric emptying. Recently, erythromycin has been linked to the occurrences of sudden cardiac death due to QT prolongation. Azithromycin is similar to erythromycin in structure but does not have significant drug-drug interactions as seen with erythromycin. PURPOSE: This study aims to determine whether azithromycin stimulates antral activity in patients with chronic gastrointestinal pain and refractory gastroparesis. METHODS: Small bowel manometric data on 30 patients undergoing clinical evaluation for chronic digestive problems or documented refractory gastroparesis were reviewed. Antral activity was measured after infusion of erythromycin 250 mg intravenous and azithromycin (500 or 250 mg intravenous) given at different intervals during the small bowel manometry. The parameters measured included the total duration of effect, mean amplitude of antral contractions, duration of the highest antral contraction phase, number of cycles per minute, and the motility index. RESULTS: Comparison of erythromycin and azithromycin at similar doses showed a similar positive effect on antral activity. However, comparison of erythromycin and azithromycin at the higher dose of 500 mg showed that the mean amplitude, duration of antral activity, and motility index were significantly increased with azithromycin (P < 0.05). CONCLUSIONS: Azithromycin stimulates antral activity similar to erythromycin and moreover has a longer duration of effect. However, unlike erythromycin, azithromycin does not have significant drug-drug interactions and maybe a potential new medication for the treatment of gastroparesis and gastrointestinal dysmotility.

[Erythromycin ethylsuccinate obtaining possibilities]. / Posibilitati de obtinere a etil-succinatului de eritromicina.

UNLABELLED: In this study we tried to improve the erythromycin ethylsuccinate obtaining, having in view to separate the erythromycin ester by crystallization in water. MATERIAL AND METHODS: The erythromycin acylation and the erythromycin ethylsuccinate crystallization were realized, following the next steps: 1. the acylation of the erythromycin with a methylene chloride solution of monoethylsuccinyl chloride, at 25-28 degrees C for 3 hours in the presence of NaHCO3; 2. the transfer of the erythromycin ethylsuccinate from methylene chloride solution in acetone solution by distillation of mixture methylene chloride: acetone 1:1 at 25-28 degrees C; 3. erythromycin ethylsuccinate separation by crystallization in water at pH = 8-8.5 and 5 degrees C for 90 minutes. The quality control for the erythromycin ester was performed according to the Xth edition of Romanian Pharmacopoeia standards using national standard for erythromycin ethylsuccinate and national standard for erythromycin with an activity of 1: 937 U and 2.02% humidity. The Micrococcus luteus ATCC 9341 was used as a test microorganism and a thin layer cromatography was performed for qualitative control. RESULTS: 13.1 g of erythromycin ethylsuccinate were obtained with an output of the process of 82.02%. Using water for the separation of erythromycin ethylsuccinate the output of the process is greater (82.02%) than in case of using petroleum ether (74.14%) or hexane (80.25%). The thin layer cromatography revealed an Rf = 0.56 and the microbiological activity of the erythromycin ethylsuccinate was 98.7% compared with the standard. CONCLUSIONS: Using water instead of hexane or petroleum ether is gainful for the separation of erythromycin ethylsuccinate from the reaction medium. The obtained erythromycin ethylsuccinate corresponds to the Xth edition of Romanian Pharmacopoeia standards. So, the raw materials consumption is decreased, the costs are cut down, the obtained product purity is high and the output of the process is greater.

Prokinetic effects of erythromycin after antimotion sickness drugs.

Motion sickness and the antimotion sickness drugs scopolamine (SCP) and promethazine (PMZ) inhibit gastric emptying (GE). This study was conducted to determine if erythromycin would exert its well-known prokinetic effects in normal and motion-sick subjects given antimotion sickness drugs. Fifteen fasted volunteers (11 males, 4 females) participated in the study. In control tests, 8 subjects were given intramuscular (i.m.) saline (SAL, 0.5 ml), SCP (0.1 mg), or PMZ (25 mg). GE of liquid (300 ml) containing 1 mCi of Tc 99m diethylenetriaminepentaacetic acid (DTPA) was measured by sequential gastric scintigraphy 30 minutes after i.m. treatments. In other tests, GE was measured in 8 subjects after each i.m. treatment, followed 10 minutes later by 200 mg of erythromycin ethylsuccinate (ESS) suspension given orally. In a third group of tests, 7 subjects received an i.m. treatment, oral EES 10 minutes later, and were then brought to an advanced level of motion sickness short of vomiting. To induce motion sickness, blindfolded subjects made timed head movements while seated in a rotating chair. GE was measured immediately after rotation. GE half-life, rate constant, area under the curve (AUC), and lag time were calculated using conventional mathematical methods for analyzing exponential rate processes. GE parameters calculated for normal and motion-sick subjects given antimotion sickness drugs and EES were compared with those from subjects given i.m. treatments (control) only. In normal subjects, EES significantly (p < 0.05) increased the GE rate constant for all i.m. treatments and reduced the AUC for SAL, SCP, and PMZ by 49% (p < 0.05), 44% (p < 0.05), and 69% (p < 0.01), respectively. In motion-sick subjects, lag time was significantly (p < 0.05) increased, and the rate constant and AUC values were unchanged from control for all i.m. treatments. The authors conclude that oral EES reverses the gastrostatic actions of the antimotion sickness drugs but does not affect the inhibition of gastric emptying associated with motion sickness. The results suggest that motion sickness and antimotion sickness drugs reduce GE through different mechanisms.

Effect of a single oral dose of two erythromycin ethylsuccinate formulations on gastric emptying in healthy volunteers: a scintigraphic study.

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.

Effects of two oral erythromycin ethylsuccinate formulations on the motility of the small intestine in human beings.

Fourteen-membered macrolides are known to produce alterations in digestive tract motor activity; these include the induction of strong gastric contractions and a decrease in the motility of the small intestine. The aim of the study was to compare the effects of two different formulations of erythromycin ethylsuccinate (EE) on duodenojejunal motility. Compared with the more commonly used crystalline formulation of EE (CEE), the amorphous formulation (AEE) has previously been described to have greater bioavailability and to induce significantly fewer gastrointestinal side effects when given at therapeutic and what have been considered to be equivalent oral doses (i.e., CEE, 1,000 mg every 12 h; AEE, 500 mg every 12 h). In a crossover double-blind study, duodenojejunal manometric recordings were performed for 10 volunteers treated with placebo, CEE at 1,000 mg, or AEE at 500 mg. Recordings for each volunteer were obtained for a fed period after a standard dinner and then for a nocturnal fasting period. When compared with the placebo, CEE significantly decreased the motility index of the duodenum during the 30 min after the peak serum erythromycin concentrations, shortened the duration of the fed state, and had no effect during the fasting state. In contrast, AEE did not significantly modify any motility parameter. Because AEE produced significantly lower concentrations in serum than CEE, these results do not necessarily imply that the two formulations of EE act differently on the motility of the small intestine.

Effect of 4 x 250 mg erythromycin on human gastrointestinal transit.

The motilin agonist erythromycin affects gastrointestinal motility. We studied its influence on gastric, intestinal, and colonic transit of indigestible solids. Ten healthy volunteers measured the gastrointestinal transit of a 6-8 mm metal sphere by metal detector with oral intake of 250 mg erythromycin q.i.d. or placebo in randomized order. Postprandial gastric emptying of the sphere after a standard meal was measured after a single i.v. dose of 250 mg erythromycin, subsequently followed by determination of small and large bowel transit. Motilin serum levels were measured for one hour. Gastric transit of the sphere was shortened from 243 +/- 34 to 72 +/- 46 min (mean +/- SD) (p = 0.002) and shifted from the interdigestive to the digestive phase. Small and large bowel transit were not influenced, and gastric transit times and motilin serum levels were not correlated. In conclusion, 250 mg erythromycin shortened postprandial gastric emptying of indigestible solids, most likely due to overcoming of pyloric sieving function by strong gastric antral contractions without effecting the transit through the lower part of the gastrointestinal tract.

Erythromycin as a prokinetic agent: a prospective, randomized, controlled study of efficacy in nasoenteric tube placement.

OBJECTIVES: Erythromycin, a macrolide antibiotic, has been shown to mimic the effects of the polypeptide motilin in the gastrointestinal tract. To determine whether erythromycin ethylsuccinate elixir would facilitate the transpyloric passage of a standard nasoenteric feeding tube once the tube was placed into the stomach, 20 patients were randomized to receive erythromycin or standard therapy. METHODS: Twenty patients (ages 45-78), mean age 63 yr, all male, had 43-inch nasoenteric tubes placed and were randomized to receive erythromycin ethylsuccinate elixir (400 mg/5 ml per os every 8 h for three doses) through the feeding tube or to receive standard therapy that involved no drug intervention. RESULTS: Three placements resulted in immediate transpyloric passage. This represented 3/21 (14%) with immediate passage. One patient dropped out after initial tube placement. The remaining 17 patients had initial tube placement in the stomach; of these, eight were randomized to receive erythromycin and nine to receive standard therapy. Six of the eight nasoenteric tubes in the erythromycin group achieved transpyloric passage in 1 day. Zero of the nine nasoenteric tubes in the standard therapy group achieved transpyloric passage in 1 day (p = 0.0023, Fisher's exact test). CONCLUSION: This study demonstrates that erythromycin ethylsuccinate elixir improves the success of transpyloric feeding tube passage in 1 day and is superior to the standard therapy, which consists of no drug intervention.

[Determination of the activity of broad-spectrum antibiotics against Mycobacterium fortuitum by the agar diffusion method]. / Opredelenie aktivnosti antibiotikov shirokogo spektra deistviia protiv Mycobacterium fortuitum metodom diffuzii v agare.

Rapidly growing M. fortuitum bring about such conditions in man, like mycobacterioses. Management of patients presents a problem since potentially pathogenic mycobacteria are highly resistant to most antituberculous drugs. To find effective antibacterial drugs for the treatment of human patients, the definition of sensitivity of M. fortuitum to broad--spectrum antibiotics by agar disk-diffusion method on Soton's medium was carried out. Sensitivity of 53 strains of mycobacteria to 13 drugs was investigated. It was demonstrated that the aminoglycoside group (gentamicin, kanamycin and monomycin inhibiting the growth of 96, 98 and 76% % of the strains, respectively) had been the most active. Tetracycline, ristomycin and erythromycin actively affected 35-15% of the tested strains. The agar disk-diffusion method is easy to handle and use in laboratory conditions.

[Sensitivity of bifidobacteria to antibacterial drugs]. / Chuvstvitel'nost' bifidobakterii k antibakterial'nym preparatam.

Twenty one strains of bifidobacteria belonging to various species were studied with respect to their sensitivity to antibacterial drugs most widely used in medical practice. The strains were isolated from practically healthy persons and from persons in contact with antibiotics in their production. It was found that sensitivity of the strains was the highest with respect to penicillins and tetracyclines. With respect to kanamycin, monomycin and levomycetin the strains were resistant. Strain differences in resistance to separate antibacterial drugs were observed. Increased streptomycin and tetracycline resistance of the strains isolated from the persons being for a prolonged period in contact with these antibiotics in their production, was stated.

[Methods of sterilizing and preserving tendon transplants]. / Sposoby sterilizatsii sukhozhil'nykh transplantatov.

The authors describe three methods for making tendon transplants by using chemical sterilizing and preserving means having no unfavorable effect on their biological and plasty properties. The methods are simple, reliable and fairly suitable for a wide supply of clinical institutions with tendon transplants.

[Antibiotic sensitivity of staphylococci associated with adenoviruses]. / Antibiotikochuvstvitel'nost' stafilokokkov v assotsiatsii s adenovirusami.

Antibiotic sensitivity to 8 staphylococcal strains was determined in artificial associations of bacteria and viruses before and after contact with adenoviruses of serotypes 2 and 7 under appropriate control. It was shown that after contact with the adenoviruses the antibiotic sensitivity of the staphylococci usually increased and they showed significant strain specificity. An attempt was made to explain the causes and mechanisms of the phenomena on the basis of the experimental and literature data.

[Dynamics of the change in sensitivity of shigellae to gentamycin and cephaloridine in vitro]. / Dinamika izmeneniia chuvstvitel'nosti shigell k gentamitsinu i tsefaloridinu in vitro.

The dynamics of the changes in the Shigella sensitivity to gentamicin and cephaloridin was studied in vitro using liquid nutrient media with gradually increasing concentrations of the drugs. 50 passages were performed. It was found that Shigella flexner and sonnei decreased their sensitivity to gentamicin to a little extent and remained middle sensitive. Sensitivity of Shigella flexner to cephaloridin also changed to a little extent, while Shigella sonnei became moderately resistant.

[Vibrion variability under the action of antibiotics]. / Izuchenie izmenchivosti vibrionov pod vliianiem antibiotikov.

Tetracycline, streptomycin and monomycin resistant variants of the cholera and NAG-vibrios were obtained by means of repeated passages on nutrient media with increasing concentrations of the antibiotics (114 variants V. cholerae asiaticae, 1337 variants of V. cholerae eltor and 299 variants of NAG-vibrios of the 1st Heiberg group). The highest number of the antibiotic resistant variants was obtained under the effect of streptomycin and the resistance level to it was much higher (up to 8000 gamma/ml) than that to tetracycline or monomycin (160 or 320 gamma/ml respectively). The study of the differential-diagnostic properties of the above vibrios showed that 14.8 per cent of the strains of V. cholerae asiaticae and 4.6 per cent of the strains of V. cholerae eltor became non-typical with respect to the colony morphology and fermentative properties. Their agglutinability with the species or type specific cholera sera partially decreased. Nine per cent out of 299 antibiotic resistant NAG-vibrios had changes only in the colony structure. None of them changed their fermentative properties or acquired even minor capacity for agglutination with cholera sera or lysing with specific bacteriophages. The described changes in the properties of the antibiotic resistant cholera and NAG-vibrios were not stable and disappeared after 2- or 3-fold passages on media containing no antibiotics.

[Properties of a collagen and monomycin complex]. / O svoistvakh kompleksa kollagena s monomitsinom

The prolonged effect of a single application of a collagen-monomycin sponge was studied experimentally on albino rats on a model of a skin flat wound. The monomycin levels in the blood and tissues in the area of the sponge application for 14 days were determined by the biological method. The therapeutically effective concentration of monomycin, i.e. 3.8 gemma/ml was maintained in the general blood flow for 2 weeks. During this period the local antibiotic concentration was almost 5 times higher. The toxic effect of the collagen-monomycin complex was studied on rabbits and albino rats for 2 months with respect to the indices of the protein metabolism and the content of residual nitrogen and urea. The activity of cholinestrerase and the content of histamine in the blood were determined. No significant changes in the studied tests were observed during the period of the chronic experiment. The microstructure of the organs of the test animals did not differ from that of the intact animals. The collagen-monomycin complex had a prolonged antibacterial effect and was not toxic with respect to the the test animal.

[Effect of antibiotic action on the submicroscopic structure of Salmonella. The action of monomycin on S. typhi]. / Effekt deistviia antibiotikov na submikroskopicheskuiu strukturu sal'monell. Deistvie monomitsina na S. typhi

The effect of subinhibitory concentrations of monomycin on the submicroscopic structures of 2 strains of S. typhi, 5 and 799 was studied. It was shown that formation of filamentoue forms, separation of the cell wall, thinning out of the cytoplasm granular component, increasing of the size of the matter with low electron optic density of fine granular structure were common in the cell response of both strains. Formation of vacuoli containing the thinned out granular component, filterable elements and complex membrane structures followed by their liberation into the medium and formation of the forms devoid of the cell walls was a characteristic peculiar property of the cell response in strain 799. The cells of strain 5 were characterized by formation of large granular osmiefilic matters and their excretion from the cells.