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PubMed1985

Erythromycin-sulfisoxazole vs amoxicillin in the treatment of acute otitis media in children. A double-blind, multiple-dose comparative study.

A fixed combination of erythromycin ethylsuccinate and sulfisoxazole acetyl (erythromycin-sulfa) was compared with amoxicillin for the treatment of acute otitis media (AOM) in children. Of 145 patients studied, 76 boys and 69 girls were compliant and were evaluated for drug efficacy (72 amoxicillin, 73 erythromycin-sulfa). Based on otoscopic and tympanometric results, cure rates at ten to 14 days for AOM due to all organisms were 83% (63/72) for amoxicillin and 89% (65/73) for erythromycin-sulfa; for Haemophilus species (including mixed infections), they were 84% for amoxicillin (26/31) and 83% for erythromycin-sulfa (20/14). Cure rates for ampicillin-resistant Haemophilus were 1/1 for amoxicillin and 7/8 (88%) for erythromycin-sulfa; one patient (12%) had persistent AOM at day 10. Of the patients with AOM due to Streptococcus pneumoniae, 82% (29/35) in the amoxicillin-treated group and 98% (39/40) in the erythromycin-sulfa-treated group were cured. Patients with S pneumoniae as the initial infecting organism who were treated with amoxicillin had significantly more clinical recurrences then their erythromycin-sulfa-treated counterparts, 66% (8/12) vs 33% (3/9). There was no difference between treatment groups in recurrence rates for patients with Haemophilus as the initial infecting organism. On the treatment day indicated, the following number of patients had middle ear effusion: by days 10 to 14, 38% (27/72) amoxicillin-treated patients and 48% (35/73) erythromycin-sulfa-treated patients; by day 28, 10% (7/71) amoxicillin-treated patients and 16% (11/70) erythromycin-sulfa-treated patients. There were no significant differences in adverse reactions. The erythromycin-sulfa combination is safe and effective treatment for AOM, including ampicillin-resistant Haemophilus.

Acute Disease↗
PubMed1998

Cardiac actions of erythromycin: influence of female sex.

CONTEXT: Erythromycin is a widely used antibiotic that infrequently causes QT-prolongation and torsades de pointes cardiac arrhythmias. For antiarrhythmic drugs, women are at a higher risk for these cardiac arrhythmias, but few other classes of drugs have been studied. OBJECTIVES: To determine whether female sex is a risk factor for cardiac arrhythmias associated with erythromycin, and if this can be correlated with in vitro measurements of the QT-response to erythromycin in male and female rabbit hearts. DESIGN: Food and Drug Administration (FDA) MEDWATCH database analysis and in vitro experiment. MAIN OUTCOME MEASURES: Cardiac arrhythmia reports associated with erythromycin from 1970 until 1996 classified by patient sex and age, and effect of female sex on erythromycin-induced QT-prolongation in isolated perfused rabbit hearts. RESULTS: We observed a sex difference in cardiac arrhythmias associated with administration of erythromycin. A total of 346 cases were found in the FDA database: 201 females (58%), 110 males (32%), and 35 unspecified (10%). Forty-nine were life-threatening ventricular arrhythmias and deaths directly related to intravenous erythromycin lactobionate: 33 women (67%) and 16 men (33%) (P=.03). During the same period, no sex imbalance was present in the prescription pattern for intravenous erythromycin lacobionate (men 47%, women 49%, unspecified 4%). Perfusion with erythromycin caused significantly greater QT-prolongation in female rabbit hearts (mean [SD], 11.8% [2.3%]) than in male hearts (6.9% [2.1%]; P = .03). CONCLUSIONS: As has been shown in reports of antiarrhythmic drugs, we found a female predominance in the FDA reports of erythromycin-associated cardiac arrhythmias. Based on in vitro experiments, a sex difference in cardiac repolarization response to erythromycin is a potential contributing factor.

Animals↗
PubMed1991

Gastrointestinal motor effects of erythromycin in humans.

The effects of an antibacterially effective IV dose of erythromycin on gastrointestinal motor activity were investigated in eight normal healthy human volunteers in the fasted state and the fed state. Motor activity was recorded by a multilumen manometric tube. Data were analyzed visually and by a computer method. Blood samples were obtained for erythromycin and motilin assays. In the gastric antrum, erythromycin significantly increased the total duration, amplitude, and area under contractions from 0 to 60 minutes and frequency of contractions from 0 to 30 minutes from the start of its infusion in the fasted state. A similar response in the fed state occurred mostly from 0 to 30 minutes after the start of erythromycin infusion. By contrast, erythromycin inhibited the frequency and decreased the duration of small intestinal contractions in the fed state but had no effect in the fasted state. The gastric motor response was related to the plasma concentration of erythromycin, but not to plasma motilin. Erythromycin significantly shortened the duration of migrating motor complex disruption by a meal. Erythromycin also induced symptoms of upper abdominal pain, bloating, and nausea. Abdominal pain was related to strong antral contractions in both fasted and fed states; bloating occurred only in the fed state. Nausea occurred in both fasted and fed states, but it was not related to any specific pattern of motor activity. It is concluded that the strong antral contractions induced by erythromycin may accelerate the rate of gastric emptying, but they may also be responsible for causing the sensations of upper abdominal pain and bloating. The motor response to erythromycin is less during the fed than during the fasted state. The strong antral contractions induced by erythromycin are not mediated by the release of motilin.

Abdominal Pain↗
PubMed1992

Erythromycin stimulates ileal motility by activation of dihydropyridine-sensitive calcium channels.

Erythromycin, a macrolide antibiotic, is a potent stimulant of small bowel motor activity (MA) which may motility either via the peptide motilin receptor or neural mechanisms. We hypothesized that erythromycin stimulates directly stimulates smooth muscle cells by a calcium-mediated event. Thus, we evaluated the effect of neuronal blockade with tetrodotoxin, muscarinic blockade with atropine, and opiate blockade with naloxone on erythromycin-stimulated MA in isolated perfused segments of rabbit terminal ileum. We also tested the effect of nonspecific calcium channel blockade (verapamil and cadmiun) and specific blockade (dihydroxypyridine and nichol) on erythromycin-stimulated MA. MA was measured with a multichannel continuous perfusion manometry catheter. Erythromycin caused a concentration-dependent increase in MA (ED100 5 x 10(-4) M). Tetrodotoxin, atropine, and naloxone did not effect erythromycin-stimulated MA (P greater than 0.05). Both verapamil (10(-7) M) and cadmium (10(-2)-10(-4) M) inhibited erythromycin-stimulated MA. Selective blockade of "l" type calcium channels using dihydropyridine (10(-6) M) and "t" channels with nickel (10(-2)-10(-4) M) both reversed erythromycin-stimulated MA. Since the isolated segments of terminal ileum were free of exogenous humoral and neural effects, these studies indicated that erythromycin directly stimulated MA in the terminal ileum. Furthermore, since tetrodotoxin, atropine, and naloxone did not inhibit this increase in MA, erythromycin acted by a mechanism which was independent of the intrinsic nervous and opiate systems. In conclusion, these data are consistent with the model that erythromycin stimulates ileal motility by a mechanism involving activation of dihydroxypyridine and nickel-sensitive calcium channels.

Animals↗
PubMed1975

Correlation between erythromycin and acid phosphatase in mouse liver.

1. Whole liver homogenates obtained from mice 1h after an intraperitoneal injection of erythromycin lactobionate (343 mg/kg, 1/3 LD 50) were fractionated into nuclear (7000 times g min), mitochondrial (33000 times g min) and lysosomr-rich (250 000 times g min) fractions. 2. The resulting fractions, as well as the final supernatant, were analyzed for erythromycin, acid phosphatase and protein. 3. The highest relative specific activities (per cent total protein) of erythromycin and of acid phosphatase were exhibited by the lysosome-rich fraction. 4. It was of interest, therefore, to examine the effects of erythromycin upon the free activity of acid phosphatase in soluble form and on its in vitro and in vivo release from liver lysosomes. 5. Concentrations of 1.7 - 10-4 M, 3.4 - 10-4 M, 6.8 - 10-4 M and 13. 6 - 10-4 M of erythromycin lactobionate had no significant effect upon the free activity of acid phosphatase in soluble form but retarded the release of this enzyme from the liver lysosome-rich preparation. This effect of erythromycin lactobionate was dose- and time-dependent. 6. Treatment of mice with erythromycin lactobionate (343 mg/kg, 1/3 LD 50) iwtraperitoneally for 7 days significantly decreased the unsedimentable acid phosphatase activity expressed as per cent of total activity in whole liver homogenates. This indicated an in vivo diminished release of acid phosphatase from liver lysosomes by erythromycin. 7. Since erythromycin lactobionate is ionisable it could be possible that erythromycin basis as many other cationic molecules accumulates in lysosomes. 8. The in vitro and in vivo diminished release of acid phosphatase may suggest that erythromycin decreases permeability of lysosomal membrane.

Acid Phosphatase↗
PubMed2006

Activity of azithromycin or erythromycin in combination with antimalarial drugs against multidrug-resistant Plasmodium falciparum in vitro.

Azithromycin, an azalide analog of erythromycin was assayed for its in vitro activity against multidrug-resistant Plasmodium falciparum K1 strain by measuring the 3H-hypoxanthine incorporation. Azithromycin caused inhibitory effects on the parasite growth with IC50 and IC90 values of 8.4+/-1.2 microM and 26.0+/-0.9 microM, respectively. Erythromycin inhibited growth of P. falciparum with IC50 and IC90 values of 58.2+/-7.7 microM and 104.0+/-10.8 microM, respectively. The activity of antimalarial drugs in combination with azithromycin or erythromycin against P. falciparum K1 were compared. Combinations of chloroquine with azithromycin or erythromycin showed synergistic effects against parasite growth in vitro. Combinations of quinine-azithromycin and quinine-erythromycin showed potentiation. Additive effects were observed in mefloquine-azithromycin and mefloquine-erythromycin combinations. Similar results were also produced by pyronaridine in combination with azithromycin or erythromycin. However, artesunate-azithromycin and artesunate-erythromycin combinations had antagonistic effects. The in vitro data suggest that azithromycin and erythromycin will have clinical utility in combination with chloroquine and quinine. The worldwide spread of chloroquine-resistant P. falciparum might inhibit the ability to treat malaria patients with chloroquine-azithromycin and chloroquine-erythromycin in areas of drug-resistant. The best drug combinations against multidrug-resistant P. falciparum are quinine-azithromycin and quinine-erythromycin.

Animals↗
PubMed2004

Mineralization of erythromycin A in aquaculture sediments.

Mineralization of erythromycin A was studied using two differently (14)C-labeled erythromycins A, which were added to aquaculture sediment samples obtained from the two salmon hatchery sites in Washington state. The added erythromycin A did not significantly alter the numbers of the total viable colonies and erythromycin-resistant bacteria. Erythromycin-resistant Pseudomonas species contained a constitutive erythromycin esterase activity contributing to the inactivation of biologically active erythromycin A in aquatic and sediment environments. The initial rate of mineralization of erythromycin A appeared to be governed by the rate of release of soil-sorbed erythromycin A. After a prolonged lag time, the S-curves of erythromycin A mineralization were observed probably because of the increase in the population density metabolizing it. This study suggests that erythromycin A is partially or completely mineralized by the sediment microbial populations.

Anti-Bacterial Agents↗
PubMed1997

The effect of intravenous erythromycin on solid meal gastric emptying in patients with chronic symptomatic post-vagotomy-antrectomy gastroparesis.

BACKGROUND: Chronic symptomatic gastroparesis occurs in 3-5% of patients following vagotomy and antrectomy. Erythromycin, a macrolide antibiotic, improves gastric emptying in patients with idiopathic and diabetic gastroparesis. Erythromycin's effect on gastric emptying in patients with post-vagotomy-antrectomy gastroparesis is unknown. The aim of this study was to determine if a single dose of intravenous erythromycin (1 mg/kg or 6 mg/kg) accelerates solid meal gastric emptying in patients with chronic symptomatic post-vagotomy-antrectomy gastroparesis. METHODS: Six patients were entered into the study, three males and three females, with a mean age of 50 years. Four patients were randomized to receive erythromycin 6 mg/kg and two patients 1 mg/kg. The mean time since initial surgery was 9.2 years (range 1-16 years) with five patients having undergone a Roux-en-Y revision. RESULTS: Intravenous erythromycin significantly lowered percentage gastric retention at 120 min, from a baseline of 90.5 +/- 6% (S.E.M.) to 40.1 +/- 4.8% after erythromycin (P = 0.0002). Erythromycin improved gastric emptying in each patient by at least 40%. Intravenous erythromycin significantly accelerated the rate of gastric emptying in the first 30 min after meal ingestion from a baseline rate of 0.072 +/- 0.06%/min to 0.96 +/- 0.31%/min after erythromycin (P = 0.028). For each of the subsequent 30 minute time periods, erythromycin had no significant effect on the rate of gastric emptying. CONCLUSION: Intravenous erythromycin significantly improves the initial phase of solid meal gastric emptying in patients with chronic symptomatic post-antrectomy-vagotomy gastroparesis.

Adult↗
PubMed2003

Uptake of erythromycin by first-feeding sockeye salmon, Oncorhynchus nerka (Walbaum), fed live or freeze-dried enriched adult Artemia or medicated pellets.

The potential to use adult Artemia to deliver erythromycin to first-feeding sockeye salmon, Oncorhynchus nerka (Walbaum), was investigated in three trials. In the first trial, first-feeding sockeye were fed live erythromycin enriched adult Artemia or pellets containing equal amounts of erythromycin for 35 days. At the end of the trial, tissue erythromycin concentration of the fish fed the live Artemia was significantly greater (P < 0.05, 25.52 +/- 1.29 microg mL(-1); mean +/- SEM), than the tissue concentration of the fish fed the pellets (0.72 +/- 0.01 microg mL(-1)). In the second trial, first-feeding sockeye were fed either live or freeze-dried bioencapsulated erythromycin (adult Artemia) or pellets containing erythromycin daily for 21 days. Mean daily erythromycin concentration in fish fed the freeze-dried Artemia, live Artemia, or pellets did not differ significantly. In the third trial, apparent erythromycin digestibility was determined. Significantly more (P < 0.05) erythromycin was retained by juvenile sockeye fed freeze-dried bioencapsulated erythromycin (98.3 +/- 1.0%) compared with medicated pellets (89.2 +/- 1.7%). Uptake of bioencapsulated erythromycin from adult Artemia (live or freeze-dried) appears to be greater than uptake from pellets. Freeze-dried and live Artemia were equally effective at delivery suggesting enriched freeze-dried adult Artemia could be produced into a highly palatable, consistent, off-the-shelf product.

Administration, Oral↗
PubMed2005

The effects of erythromycin on the viability and the secretion of TNF-alpha and TGF-beta1 and expression of connexin43 by human pleural mesothelial cells.

OBJECTIVE: The mechanism by which erythromycin produces pleurodesis remains unknown. The purpose of this study was to investigate the effects of erythromycin on human pleural mesothelial cell (HPMC) viability, the secretion of tumour necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta(1) (TGF-beta(1)) and the level of expression of connexin43. METHODOLOGY: HPMC were incubated with different concentrations of erythromycin. The inhibitory effects of erythromycin on HPMC growth were measured using a tetrazolium-based colorimetric assay. The levels of TNF-alpha and TGF-beta(1) in supernatants were measured by ELISA and levels of connexin43 were assessed by Western blot. RESULTS: Erythromycin injured HPMC in a dose and time-dependent manner. The secretion of both TNF-alpha and TGF-beta(1) by HMPC increased significantly when they were incubated with 100 mg/L erythromycin for 3 or 5 days. The levels of connexin43 in HPMC decreased after incubation with 100 mg/L erythromycin and no relationship was observed between the levels and incubation time. CONCLUSIONS: Erythromycin injures HPMC in a dose- and time-dependent manner and results in the secretion of TNF-alpha and TGF-beta(1). This is one possible mechanism of pleurodesis with erythromycin. Furthermore, erythromycin decreased the levels of connexin43 in HPMC, which could possibly affect the response of HPMC to pleurodesis with erythromycin.

Analysis of Variance↗
PubMed2000

The stimulation of antral motility by erythromycin is attenuated by hyperglycemia.

OBJECTIVE: Diabetic gastroparesis is usually treated with prokinetic drugs, of which the most potent, when given intravenously during euglycemia, is erythromycin. Recent studies have demonstrated that the gastrokinetic effects of erythromycin are attenuated by hyperglycemia. The aim of this study was to determine whether the effects of erythromycin on antropyloroduodenal motility, including the organization of antral pressure waves, are modified by hyperglycemia. METHODS: A total of eight healthy male volunteers (median age 24 yr) were studied on 2 days each in randomized order. A manometric assembly, incorporating six antral, two pyloric, and seven duodenal sideholes and a pyloric sleeve sensor, was positioned with the sleeve spanning the pylorus. The blood glucose concentration was stabilized at about 5 mmol/L (euglycemia) or 15 mmol/L (hyperglycemia). After 30 min (T = 0), an intraduodenal lipid infusion (1.5 kcal/min) was commenced and continued until the end of the study. At T = 20 minutes, erythromycin (200 mg) as the lactobionate was infused intravenously over 20 min, followed by 100 mg over the next 40 min. RESULTS: Intravenous erythromycin increased the amplitude of antral waves during intraduodenal lipid infusion at both blood glucose concentrations (p < 0.01 for euglycemia and p < 0.05 for hyperglycemia). After erythromycin (T = 20 to T = 80), the frequency (p < 0.05) and amplitude (p < 0.01) of antral waves were less during hyperglycemia than euglycemia. Both propagated (p < 0.0005) and nonpropagated (p < 0.01) antral waves were decreased by hyperglycemia, but the suppression of propagated waves was greater (p < 0.05). Erythromycin reduced the frequency (p = 0.09) but increased the amplitude (p < 0.05) of phasic pyloric pressures, and decreased basal pyloric pressure (p < 0.0005). The frequency (p = 0.06) and amplitude (p < 0.05) of phasic pyloric waves during erythromycin infusion were slightly less during hyperglycemia than euglycemia, whereas there was no effect of the blood glucose concentration on basal pyloric pressure. Erythromycin increased the amplitude (p < 0.001) but not the frequency of duodenal waves; the frequency and amplitude of duodenal waves did not differ between the two blood glucose concentrations. CONCLUSIONS: Hyperglycemia attenuates the stimulation of antral pressures and propagated antral sequences by erythromycin, but not the effects of erythromycin on pyloric or duodenal motility.

Adolescent↗
PubMed2006

Natural transformation-mediated transfer of erythromycin resistance in Campylobacter coli strains from turkeys and swine.

Erythromycin resistance in Campylobacter coli from meat animals is frequently encountered and could represent a substantial barrier to antibiotic treatment of human infections. Erythromycin resistance in this organism has been associated with a point mutation (A2075G) in the 23S rRNA gene. However, the mechanisms responsible for possible dissemination of erythromycin resistance in C. coli remain poorly understood. In this study, we investigated transformation-mediated acquisition of erythromycin resistance by genotypically diverse C. coli strains from turkeys and swine, with total genomic DNA from erythromycin-resistant C. coli of either turkey or swine origin used as a donor. Overall, transformation to erythromycin resistance was significantly more frequent in C. coli strains from turkeys than in swine-derived strains (P < 0.01). The frequency of transformation to erythromycin resistance was 10(-5) to 10(-6) for turkey-derived strains but 10(-7) or less for C. coli from swine. Transformants harbored the point mutation A2075G in the 23S rRNA gene, as did the erythromycin-resistant strains used as DNA donors. Erythromycin resistance was stable in transformants following serial transfers in the absence of the antibiotic, and most transformants had high MICs (>256 microg/ml), as did the C. coli donor strains. In contrast to the results obtained with transformation, spontaneous mutants had relatively low erythromycin MICs (32 to 64 microg/ml) and lacked the A2075G mutation in the 23S rRNA gene. These findings suggest that natural transformation has the potential to contribute to the dissemination of high-level resistance to erythromycin among C. coli strains colonizing meat animals.

Animals↗
PubMed1983

Intracellular multiplication of Legionnaires' disease bacteria (Legionella pneumophila) in human monocytes is reversibly inhibited by erythromycin and rifampin.

We have previously reported that virulent egg yolk-grown Legionella pneumophila, Philadelphia 1 strain, multiplies intracellularly in human blood monocytes and only intracellularly under tissue culture conditions. In this paper, we have investigated the effect of erythromycin and rifampin on L. pneumophila-monocyte interaction in vitro; erythromycin and rifampin are currently the drugs of choice for the treatment of Legionnaires' disease. The intracellular multiplication of L. pneumophila is inhibited by erythromycin and rifampin, as measured by colony-forming units, whether the antibiotics are added just before or just after infection of monocytes with L. pneumophila, or 2 d after infection when L. pneumophila is in the logarithmic phase of growth in monocytes. Intracellular multiplication of L. pneumophila is inhibited by 1.25 microgram/ml but not less than or equal to 0.125 microgram/ml erythromycin and 0.01 microgram/ml but not less than or equal to 0.001 microgram/ml rifampin. These concentrations of antibiotics are comparable to those that inhibit extracellular multiplication of L. pneumophila under cell-free conditions in artificial medium; the minimal inhibitory concentration is 0.37 microgram/ml for erythromycin and 0.002 microgram/ml for rifampin. Multiplication of L. pneumophila in the logarithmic phase of growth in monocytes is inhibited within 1 h of the addition of antibiotics. Intracellular bacteria inhibited from multiplying by antibiotics are not killed. By electron microscopy, the bacteria appear intact within membrane-bound vacuoles, studded with ribosomelike structures. L. pneumophila multiplying extracellularly on artificial medium is killed readily by relatively low concentrations of erythromycin and rifampin; the minimal bactericidal concentration is 1 microgram/ml for erythromycin and 0.009 microgram/ml for rifampin. In contrast, L. pneumophila multiplying intracellularly is resistant to killing by these concentrations of erythromycin and rifampin or by concentrations equal to or greater than peak serum levels in humans. Extracellular L. pneumophila in stationary phase is also resistant to killing by erythromycin and rifampin. These findings, taken together with our previous work, indicate that, in vivo, L. pneumophila is resistant to killing by erythromycin and rifampin. Inhibition of L. pneumophila multiplication in monocytes by antibiotics is reversible; when the antibiotics are removed from infected monocyte cultures after 2 d, L. pneumophila resumes multiplication. This study indicates that patients with Legionnaires' disease under treatment with erythromycin and rifampin require host defenses to eliminate L. pneumophila, and that inadequate host defenses may result in relapse after cessation of therapy.

Cells, Cultured↗
PubMed2001

Erythromycin and common cold in COPD.

STUDY OBJECTIVES: To investigate whether erythromycin therapy lowers the frequency of the common cold and subsequent exacerbation in patients with COPD. DESIGN: Prospective, randomized, controlled, but not blinded, trial. PATIENTS: One hundred nine patients with COPD were enrolled into the study. Patients were randomly assigned to erythromycin therapy or to no active treatment in September 1997. Patients then were observed for 12 months, starting in October, during which time the risk and frequency of catching common colds and COPD exacerbations were investigated. Fifty-five patients received erythromycin at study entry (erythromycin group). The remaining 54 patients received no active treatment (control group). MEASUREMENTS AND RESULTS: The mean (+/- SE) number of common colds for 12 months was significantly lower in the erythromycin group than in the control group (1.24 +/- 0.07 vs 4.54 +/- 0.02, respectively, per person; p = 0.0002). Forty-one patients (76%) in the control group experienced common colds more than once, compared to 7 patients (13%) in the erythromycin group. The relative risk of developing two or more common colds in the control group compared with that in the erythromycin group was 9.26 (95% confidence interval [CI], 3.92 to 31.74; p = 0.0001). Thirty patients (56%) in the control group and 6 patients (11%) in the erythromycin group had one or more exacerbations. The relative risk of experiencing an exacerbation in the control group compared with that in the erythromycin group was 4.71 (95% CI, 1.53 to 14.5; p = 0.007). Significantly more patients were hospitalized due to exacerbations in the control group than in the erythromycin group (p = 0.0007). CONCLUSION: Erythromycin therapy has beneficial effects on the prevention of exacerbations in COPD patients.

Aged↗
PubMed2005

Lack of pharmacokinetic drug-drug interaction between ciclesonide and erythromycin.

OBJECTIVE: To investigate whether systemic exposure to desisobutyrylciclesonide (des-CIC) (the pharmacologically active metabolite of ciclesonide) and erythromycin are affected by combined administration of ciclesonide and erythromycin. METHODS: 18 healthy subjects were enrolled in a Phase 1, open-label, randomized, three-period crossover study. Each subject received ciclesonide (640 microg ex-actuator, equivalent to 800 microg ex-valve, via hydrofluoroalkane metered-dose inhaler) and erythromycin (500 mg PO), separately and in combination, in random order. Blood samples were collected at timed intervals to determine serum concentrations of erythromycin, des-CIC, and ciclesonide using HPLC-MS detection. Adverse events were recorded throughout the study. RESULTS: Combined administration of ciclesonide and erythromycin did not alter the pharmacokinetics (PK) of either drug. The serum concentration vs. time profiles of erythromycin, des-CIC, and ciclesonide were similar when ciclesonide and erythromycin were administered separately or together. In addition, the PK characteristics of erythromycin and des-CIC were equivalent following single or co-administration. Point estimates (90% confidence intervals (CI)) for erythromycin were as follows: AUC0-inf, 0.96 (0.79, 1.18); Cmax, 1.00 (0.84, 1.20); and t1/2, 0.96 (0.83, 1.12). The following point estimates (90% CI) were obtained for des-CIC: AUC0-inf, 1.16 (1.03, 1.30); Cmax, 1.06 (0.98, 1.15); and t1/2, 1.04 (0.96, 1.13). Lack of ciclesonide/erythromycin interaction was demonstrated as the 90% CI of AUC0-inf, Cmax, and t1/2 of both compounds were entirely within the stipulated equivalence range of 0.67 - 1.50. No study drug-related adverse events occurred during this study. CONCLUSIONS: Combined administration of ciclesonide and erythromycin did not alter the PK properties of either drug. Both drugs were safe and well-tolerated. Therefore, systemic exposure to ciclesonide or erythromycin is not increased in patients receiving concomitant therapy.

Adolescent↗
PubMed2001

Early postoperative erythromycin breath test correlates with hepatic cytochrome P4503A activity in liver transplant recipients.

BACKGROUND: Interindividual variation in the pharmacokinetics of the immunosuppressive agents cyclosporine (INN, ciclosporin) and tacrolimus may result from differences in the activity of cytochrome P4503A (CYP3A). The erythromycin breath test is an in vivo assay of hepatic CYP3A activity, but the method has never been directly validated. The aim of the study was to investigate whether an early postoperative erythromycin breath test correlated with the hepatic CYP3A protein level and catalytic activity in liver transplant recipients. METHODS: In 18 liver transplant recipients, the erythromycin breath test was performed within 2 hours after transplantation. A graft biopsy was obtained during surgery and analyzed for the CYP3A protein level by Western blotting and for CYP3A activity with erythromycin demethylation and testosterone 6beta- hydroxylation assays. RESULTS: The erythromycin breath test values ranged from 0.14% to 1.65% of carbon 14 per hour, and the CYP3A protein level ranged from 732 to 7822 as measured by optical density. The in vitro catalytic activity determined by the erythromycin demethylation assay ranged from 94 to 902 disintegrations per minute per 5 minutes per milligram of protein, and the activity determined by testosterone 6beta-hydroxylation ranged from 0.030 to 0.627 nmol per minute per milligram of protein. Significant correlation was demonstrated between the erythromycin breath test and both the erythromycin demethylation (Spearman correlation coefficient: R = 0.76, R (2) = 0.57; P =.0004) and the testosterone 6beta-hydroxylation (Spearman correlation coefficient: R = 0.79, R (2) = 0.63; P =.0001) assays. The erythromycin breath test also correlated with the CYP3A protein level (Spearman correlation coefficient: R = 0.60, R (2) = 0.36; P =.01). CONCLUSION: Our data support the erythromycin breath test as a specific in vivo assay of CYP3A activity in humans. The test is applicable in liver transplant recipients in the early postoperative phase. Future studies should evaluate the clinical usefulness of an early postoperative erythromycin breath test as a predictor of cyclosporine-tacrolimus pharmacokinetics in liver transplantation.

Adolescent↗
PubMed1981

Self-induction by erythromycin of its own transformation into a metabolite forming an inactive complex with reduced cytochrome P-450.

Erythromycin, 0.3 mM, elicited a small reverse type I binding spectrum with, and was slowly demethylated by, cytochrome P-450 from control rats. No absorption peak at 456 nm could be detected upon incubation of 0.3 mM erythromycin with NADPH and control microsomes. No complex formed in vivo could be detected in microsomes isolated 2 hr after a single dose of erythromycin, 2 mmol.kg-1 p.o. Repeated administration of erythromycin, 2 mmol.kg-1 p.o. daily for 4 days increased hepatic microsomal protein concentration, NADPH-cytochrome c reductase activity, the amplitude of the reverse type I binding spectrum of erythromycin and erythromycin demethylase activity. Microsomes isolated from rats treated with repeated doses of erythromycin exhibited a marked absorption peak at 456 nm. The absorption at 456 nm was further increased upon incubation with erythromycin and NADPH. It disappeared upon addition of 50 muM potassium ferricyanide. Disruption of the complex with potassium ferricyanide markedly increased the CO-binding capacity of dithionite-reduced microsomes. It further increased the amplitude of the reverse type I binding spectrum of erythromycin and erythromycin demethylase activity and increased ethylmorphine N-demethylase and benzo[a]pyrene hydroxylase activities. It is concluded that erythromycin induces its own transformation into a metabolite which forms a inactive 456-nm absorbing complex with the iron (II) of cytochrome P-450.

Animals↗
PubMed1993

The treatment of idiopathic and diabetic gastroparesis with acute intravenous and chronic oral erythromycin.

The objective of this study was to investigate the effects of intravenous erythromycin and chronic oral dosing of erythromycin on gastric emptying in patients with idiopathic or diabetic gastroparesis. Symptoms were assessed on oral dosing and during long-term follow-up in an ambulatory setting at a University referral center. Fourteen patients (10 idiopathic and four diabetic gastroparesis) were studied. Four patients left during the 4-wk study; two due to rash, one with cramps and vomiting on erythromycin, and one due to other medical problems. Ten patients completed the 4-wk study and commenced long-term therapy. Five of these patients experienced enough symptomatic relief to continue oral erythromycin long-term, being followed for an average period of 8.4 months. After initial documentation of delayed gastric emptying, patients received 6 mg/kg intravenous erythromycin lactobionate before a second gastric emptying study. Erythromycin base was then given orally at a dose of 500 mg tid-ac and qhs, with a final gastric emptying study performed after 4 wk. During long-term follow-up, erythromycin dosage was adjusted to minimize symptoms. Radionuclide-labeled gastric emptying of a solid meal was studied at baseline, following intravenous erythromycin, and after 4 wk of oral treatment with erythromycin. Symptom scores were assessed at baseline, at 4 wk, and then at 8-wk intervals. The percentage of the solid meal retained in the stomach at 2 h decreased from 85% +/- 11% (SD) at baseline to 20% +/- 29% following intravenous erythromycin (p < 0.001), and to 48% +/- 21% after 4 wk of oral therapy (p < 0.01 vs. baseline). There was a reduction in total symptom scores and a significant reduction in global assessment scores (p = 0.03). We conclude that erythromycin has a strong gastric prokinetic effect in both idiopathic and diabetic gastroparesis, and may represent a useful new therapeutic approach to this problem.

Administration, Oral↗