A Phase I Determination of Azithromycin in Plasma during a 6-Week Period in Normal Volunteers after a Standard Dose of 500mg Once Daily for 3 Days

Crokaert, Françoise; Hubloux, A.; Cauchie, Philippe

doi:10.2165/00044011-199816020-00009

Cited by 25 publications

(19 citation statements)

References 13 publications

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“…Secondly, faecal, blood and rectal mucus contamination could have affected our results. Blood levels of azithromycin have been shown to be undetectable after 24 hours [13] or present at very low levels [38] so blood contamination is more likely to affect concentrations measured within 24 hours post dose, such as what might have been seen in participant 4 (2 hour post dose tissue concentration of 453.3mcg/mL vs median of 3.0mcg/mL for other participants). Approximately 47% of azithromycin is excreted in faeces in the first 24 hours [18] so this could affect samples taken within 48 hours of taking azithromycin but is less likely to impact on results after this time.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of a single 1g dose of azithromycin in rectal tissue in men

et al. 2017

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Chlamydia is the most common bacterial sexually transmitted infection among men who have sex with men. Repeat infection following treatment with 1g azithromycin is common and treatment failure of up to 22% has been reported. This study measured the pharmacokinetics of azithromycin in rectal tissue in men following a single 1g dose to assess whether azithromycin reaches the rectal site in adequate concentrations to kill chlamydia. Ten healthy men took a single oral dose of 1g azithromycin and provided nine self-collected swabs and one blood sample over 14 days. Participant demographics, medications, sexual behaviour, treatment side effects, lubricant use and douching practices were recorded with each swab. Drug concentration over time was determined using liquid chromatography–mass spectrometry and total exposure (AUC0-∞) was estimated from the concentration-time profiles. Following 1g of azithromycin, rectal concentrations peaked after a median of 24 hours (median 133mcg/g) and remained above the minimum inhibitory concentration for chlamydia (0.125mcg/mL) for at least 14 days in all men. AUC0-∞ was the highest ever reported in human tissue (13103((mcg/g).hr)). Tissue concentrations were not associated with weight (mg/kg), but data suggest that increased gastric pH could increase azithromycin levels and diarrhoea or use of water-based lubricants could decrease concentrations. High and sustained concentrations of azithromycin were found in rectal tissue following a single 1g dose suggesting that inadequate concentrations are unlikely to cause treatment failure. Factors effecting absorption (pH and diarrhoea) or drug depletion (douching and water-based lubricants) may be more important determinants of concentrations in situ.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of a single 1g dose of azithromycin in rectal tissue in men

et al. 2017

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“…Azithromycin has a long elimination half-life of approximately 66 h (34). Importantly, this half-life is longer for azithromycin than for all other antibiotics utilized in COPD patients and may lead to drug concentrations well below the MIC for up to 30 days (34,35). Prolonged and subinhibitory antibiotic concentrations are likely to provide an optimal environment for the We eliminated from analysis 14 strains that we could not confirm as recentacquisition isolates; 11 were present at the first study clinic visit, and two were isolated from participants with more than three missing visits prior to strain isolation.…”

Section: Discussionmentioning

confidence: 99%

Effect of Fluoroquinolones and Macrolides on Eradication and Resistance of Haemophilus influenzae in Chronic Obstructive Pulmonary Disease

Pettigrew

Tsuji

Gent³

et al. 2016

Antimicrob Agents Chemother

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Little is known about the effect of antibiotics on eradication of carriage and development of resistance in Haemophilus influenzae in individuals with chronic obstructive pulmonary disease (COPD). Our goals were to assess antibiotic susceptibilities, prevalence of resistance genes, and development of resistance in H. influenzae and to evaluate the effect of macrolide and fluoroquinolone administration on H. influenzae eradication. Data were from a 15-year longitudinal study of COPD. Genome sequence data were used to determine genotype and identify resistance genes. MICs of antibiotics were determined by reference broth microdilution. Generalized linear mixed models were used to evaluate associations between antibiotic use and H. influenzae eradication. We examined 267 H. influenzae isolates from 77 individuals. All newly acquired H. influenzae isolates were susceptible to azithromycin. C hronic obstructive pulmonary disease (COPD) affects approximately 24 million people in the United States and is the third leading cause of death worldwide (1, 2). Disease is characterized by intermittent acute exacerbations of COPD (AECOPD) that result in missed work, clinic visits, emergency room visits, hospital admissions, and respiratory failure requiring mechanical ventilation. Approximately half of AECOPD cases are caused by bacterial infection, with nontypeable Haemophilus influenzae being the most common pathogen (3, 4). H. influenzae also colonizes the lower airways of individuals with COPD for extended periods and contributes to inflammation, impaired pulmonary function, and increases in daily respiratory symptoms (3-6).Clinical studies indicate that antibiotic therapy results in accelerated recovery and reduced complications of moderate and severe exacerbations (7,8). Thus, antibiotics, particularly oral macrolides and fluoroquinolones, are commonly prescribed for treatment of AECOPD (4,(8)(9)(10). Several recent clinical trials demonstrated that daily azithromycin results in fewer exacerbations and improved quality of life, and thus, azithromycin is increasingly administered prophylactically to many COPD patients (11)(12)(13).In spite of widespread administration of antibiotics for treatment and prophylaxis of infection in COPD, remarkably little is known about the effect of antibiotics on carriage and eradication of respiratory tract pathogens, particularly H. influenzae. Prior studies suggested that fluoroquinolones were superior to macrolides in eradicating H. influenzae (14-17). However, a significant limitation of these studies is that eradication was assumed if the patient was unable to produce sputum and/or was determined by a single posttreatment sputum culture. This study design misses the possibility of H. influenzae persistence in spite of negative culture, a scenario known to be common in COPD (3). When microbiologic confirmation was obtained, the strains were not genotyped, precluding determination of whether a positive culture represented unsuccessful bacterial eradication or acquisition of a new strain...

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“…The higher rates of macrolide resistance with azithromycin are consistent with prior data linking increases in population Streptococcus pneumoniae macrolide resistance rates to increasing consumption of azithromycin, [11][12][13]27 an effect implied by its long half-life, which allows for extended periods of subinhibitory concentrations. 28 In the absence of a direct randomized controlled trial comparison of long-term azithromycin and erythromycin, it is not possible to unequivocally conclude that erythromycin use is preferable because it induces less resistance, although all available data support that interpretation.…”

Section: Commentmentioning

confidence: 99%

Effect of Long-term, Low-Dose Erythromycin on Pulmonary Exacerbations Among Patients With Non–Cystic Fibrosis Bronchiectasis

Serisier¹,

Martin²,

McGuckin³

et al. 2013

JAMA

368

352

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HE PATHOPHYSIOLOGY OF NONcystic fibrosis (CF) bronchiectasis is generally considered to be characterized by an airway inflammatory response to bacterial pathogens, and recent data provide further evidence to support this "vicious cycle" hypothesis. 1 However, studies of maintenance therapies designed to interrupt this cycle at differing points have failed to demonstrate convincing evidence of clinical efficacy, including prolonged oral antibiotics, 2 inhaled tobramycin, 3 inhaled corticosteroids, 4 and mucolytics. 5 Until recently, 6 there have arguably been no therapies with proven clinical benefit in non-CF bronchiectasis.Maintenance azithromycin was shown to reduce exacerbations in non-CF bronchiectasis 6 ; however, limitations of that study 7 included a treatment period of only 6 months and a lack of systematic evaluation for macrolide See also pp 1251 and 1295.

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A Phase I Determination of Azithromycin in Plasma during a 6-Week Period in Normal Volunteers after a Standard Dose of 500mg Once Daily for 3 Days

Abstract: In conclusion, the utility of the long exposure of patients with benign respiratory infections to azithromycin and to subinhibitory concentrations of azithromycin should be questioned.

Cited by 25 publications

References 13 publications

Pharmacokinetics of a single 1g dose of azithromycin in rectal tissue in men

Pharmacokinetics of a single 1g dose of azithromycin in rectal tissue in men

Effect of Fluoroquinolones and Macrolides on Eradication and Resistance of Haemophilus influenzae in Chronic Obstructive Pulmonary Disease

Effect of Long-term, Low-Dose Erythromycin on Pulmonary Exacerbations Among Patients With Non–Cystic Fibrosis Bronchiectasis

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