The diffusion of clarithromycin and roxithromycin into nasal mucosa, tonsil and lung in humans

Fraschini, F.; Scaglione, F; Pintucci, Giuseppe; Maccarinelli, Giuseppina; Dugnani, S.; Demartini, G.

doi:10.1093/jac/27.suppl_a.61

Cited by 98 publications

(40 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In one earlier study [8], the concentration of clarithromycin reached a peak in various tissues, including whole lung, 4 h after oral administration of 500 mg b.i.d. for 3 days.…”

Section: Discussionmentioning

confidence: 88%

See 1 more Smart Citation

The levels of clarithromycin and its 14-hydroxy metabolite in the lung

Honeybourne¹,

Kees²,

Andrews³

et al. 1994

Eur Respir J

View full text Add to dashboard Cite

T Th he e l le ev ve el ls s o of f c cl la ar ri it th hr ro om my yc ci in n a an nd d i it ts s 1 14 4--h hy yd dr ro ox xy y m me et ta ab bo ol li it te e i in n t th he e l lu un ng g ABSTRACT: Clarithromycin is a new macrolide that has a longer half-life than erythromycin and is claimed to reach higher tissue concentrations. We aimed to investigate whether, following oral administration, the drug and its 14-hydroxy metabolite reach levels in lung tissue that are likely to be clinically effective against common respiratory pathogens. Ten patients undergoing diagnostic bronchoscopy received seven doses of clarithromycin, 500 mg b.i.d. orally. Bronchoscopy was performed at a mean time of 4.25 h after the last dose. At bronchoscopy, bronchial biopsies and bronchoalveolar lavage were performed. Clarithromycin and its 14-OH metabolite were measured in serum, bronchial biopsies, epithelial lining fluid (ELF) and alveolar cells.Mean levels of clarithromycin were 4.0 mg·l -1 in serum, 16.8 mg·kg in bronchial biopsies, 20.5 mg·l -1 in ELF and 372.7 mg·l -1 in alveolar cells. The equivalent levels of 14-OH metabolite were 0.7, 2.7, 1.9 and 38.6 mg·l -1 , respectively.We conclude that there is considerable concentration of clarithromycin and its 14-OH metabolite in alveolar cells, and to a lesser extent in bronchial tissue and ELF; this implies efficacy against susceptible organisms at these sites.

show abstract

“…In one earlier study [8], the concentration of clarithromycin reached a peak in various tissues, including whole lung, 4 h after oral administration of 500 mg b.i.d. for 3 days.…”

Section: Discussionmentioning

confidence: 88%

“…Azithromycin [16] has also been found to be concentrated in lung tissues. Roxithromycin, however, is not concentrated in lung tissues to the same extent [8]. One study in humans showed levels of clarithromycin of 17.5 mg·kg -1 in whole lung tissue with a serum level D. HONEYBOURNE ET AL.…”

Section: Discussionmentioning

confidence: 99%

The levels of clarithromycin and its 14-hydroxy metabolite in the lung

Honeybourne¹,

Kees²,

Andrews³

et al. 1994

Eur Respir J

View full text Add to dashboard Cite

show abstract

“…Multidrug resistance complicates therapeutic options for the clinician. Indeed, patients infected with multidrug-resistant M. tuberculosis must be treated for a much longer period of time than are patients infected with susceptible strains and response rates are decreased (7,9,12,19).Clarithromycin is a new, acid-stable macrolide antibiotic which has good bioavailability after oral dosing (11,15,25). Peak serum and lung clarithromycin concentrations are 2 to 4 g/ml and 17.5 g/g, respectively (11, 15).…”

mentioning

confidence: 99%

“…Clarithromycin is a new, acid-stable macrolide antibiotic which has good bioavailability after oral dosing (11,15,25). Peak serum and lung clarithromycin concentrations are 2 to 4 g/ml and 17.5 g/g, respectively (11, 15).…”

mentioning

confidence: 99%

Synergistic activities of clarithromycin and antituberculous drugs against multidrug-resistant Mycobacterium tuberculosis

Cavalieri

Biehle

Sanders

1995

Antimicrob Agents Chemother

View full text Add to dashboard Cite

The rise of multidrug-resistant Mycobacterium tuberculosis has complicated therapy for tuberculosis and led us to search for a potentially active combination of drugs against these strains. The susceptibilities of 12 strains of multidrug-resistant M. tuberculosis to standard antituberculous drugs (isoniazid, rifampin, ethambutol, and pyrazinamide), clarithromycin, and its metabolite, 14-hydroxyclarithromycin, were determined by use of the BACTEC radiometric method. All strains were resistant to at least two of the antituberculous drugs. Clarithromycin and 14-hydroxyclarithromycin MICs were in the range indicating resistance at >8.0 g/ml for all strains. Combination testing by the BACTEC method was performed with various concentrations of isoniazid, rifampin, and ethambutol, and with clarithromycin/14-hydroxyclarithromycin at fixed concentrations of 2.0/0.5 g/ml, respectively. Addition of clarithromycin/14-hydroxyclarithromycin to these antituberculous drug mixtures resulted in a 4-to 32-fold reduction in MICs of isoniazid, rifampin, and ethambutol and made resistant strains susceptible. Fractional inhibitory concentrations ranged from 0.23 to 0.50 for all strains, suggesting a synergistic interaction between standard antituberculous drugs and clarithromycin/14-hydroxyclarithromycin. The ability of clarithromycin/14-hydroxyclarithromycin to enhance the activities of isoniazid, ethambutol, and rifampin in vitro suggests that this combination may be efficacious in the treatment of multidrug-resistant M. tuberculosis infections.In recent years there has been renewed interest in infections caused by Mycobacterium tuberculosis. This has been due in part to the resurgence of tuberculosis cases nationwide and an alarming increase in multidrug resistance in M. tuberculosis isolates from these infections (2,5,6,12,14,27,29). Multidrug resistance in M. tuberculosis is especially prevalent in certain geographic localities in the United States, including New York City and Florida (2,9,12,14,29). In addition, certain populations, including those infected with human immunodeficiency virus, recent immigrants to the United States, and patients with a history of treatment for tuberculosis (2,10,14,19,27), have an increased incidence. Most of these strains are resistant to the primary antituberculous drugs isoniazid and/or rifampin (2,10,12,29). Multidrug resistance complicates therapeutic options for the clinician. Indeed, patients infected with multidrug-resistant M. tuberculosis must be treated for a much longer period of time than are patients infected with susceptible strains and response rates are decreased (7,9,12,19).Clarithromycin is a new, acid-stable macrolide antibiotic which has good bioavailability after oral dosing (11,15,25). Peak serum and lung clarithromycin concentrations are 2 to 4 g/ml and 17.5 g/g, respectively (11, 15). Clarithromycin is metabolized to 14-hydroxyclarithromycin, which also has antibacterial activity and may act synergistically with the parent compound (18, 25). Clarithromycin has broad-spectr...

show abstract

“…The excellent tissue levels of the new macrolides, less frequent dosing, and broad spectrum activity make them ideal agents in the treatment of community-acquired bacterial respiratory infections, uncomplicated soft tissue infections, and sexually transmitted diseases (11)(12)(13)(14)(15)(16)(17). In numerous clinical trials they have been found to be as effective as the currently available oral antibiotics.…”

Section: Macrolides Available In the Unitedmentioning

confidence: 99%