Tear concentrations of azithromycin following topical administration of a single dose of azithromycin 0.5%, 1.0%, and 1.5% eyedrops (T1225) in healthy volunteers

Frédéric Chiambaretta, R. Garraffo, P. P. Elena, P. Pouliquen, L. Delval, D. Rigal, C. Dubray, P. Goldschmidt, K. Tabbara, I. Cochereau

Research output: Contribution to journalArticle

Abstract

PURPOSE. To evaluate azithromycin tear concentrations after one drop of T1225 0.5%, 1.0%, and 1.5% eyedrops. METHODS. In this randomized, double-masked study, 91 healthy volunteers received one drop into each eye of T1225 0.5% (n=23), T1225 1.0% (n=38), or T1225 1.5% (n=38). Azithromycin tear concentrations were measured by HPLC-MS at seven time points for 24 hours. Tolerability was evaluated. RESULTS. T1225 1.0% and 1.5% had similar pharmacokinetic profiles. After a post-instillation peak (167 to 178 mg/L after 10 minutes), mean concentrations remained above 7 mg/L for 24 hours (except for T1225 1% at H24). A delayed increase of the azithromycin mean tear concentration might be explained by the known late azithromycin release from tissues after storage in cells. Areas under inhibitory curve (AUICs) of T1225 1.0% and 1.5% were higher than AUICs of T1225 0.5% and ranged between 47 and 90. The three T1225 concentrations were safe for the ocular surface. CONCLUSIONS. Once daily instillation of T1225 1.0% and 1.5% was shown to reach an AUIC markedly above the required threshold for an antibacterial activity against Gram-positive bacteria (25-35). These results suggest that a BID instillation is more likely to ensure antimicrobial activity against Gram-negative bacteria (threshold >100).

Original languageEnglish (US)
Pages (from-to)13-20
Number of pages8
JournalEuropean Journal of Ophthalmology
Volume18
Issue number1
StatePublished - Jan 2008
Externally publishedYes

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Topical Administration
Azithromycin
Ophthalmic Solutions
Tears
Healthy Volunteers
Area Under Curve
Gram-Positive Bacteria
Gram-Negative Bacteria
Double-Blind Method
Pharmacokinetics
High Pressure Liquid Chromatography

Keywords

  • Area under the inhibitory curve (AUIC)
  • Azithromycin eyedrops
  • Minimal inhibitory concentration (MIC)
  • T1225
  • Tear pharmacokinetics/pharmacodynamics

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Tear concentrations of azithromycin following topical administration of a single dose of azithromycin 0.5%, 1.0%, and 1.5% eyedrops (T1225) in healthy volunteers. / Chiambaretta, Frédéric; Garraffo, R.; Elena, P. P.; Pouliquen, P.; Delval, L.; Rigal, D.; Dubray, C.; Goldschmidt, P.; Tabbara, K.; Cochereau, I.

In: European Journal of Ophthalmology, Vol. 18, No. 1, 01.2008, p. 13-20.

Research output: Contribution to journalArticle

Chiambaretta, F, Garraffo, R, Elena, PP, Pouliquen, P, Delval, L, Rigal, D, Dubray, C, Goldschmidt, P, Tabbara, K & Cochereau, I 2008, 'Tear concentrations of azithromycin following topical administration of a single dose of azithromycin 0.5%, 1.0%, and 1.5% eyedrops (T1225) in healthy volunteers', European Journal of Ophthalmology, vol. 18, no. 1, pp. 13-20.
Chiambaretta, Frédéric ; Garraffo, R. ; Elena, P. P. ; Pouliquen, P. ; Delval, L. ; Rigal, D. ; Dubray, C. ; Goldschmidt, P. ; Tabbara, K. ; Cochereau, I. / Tear concentrations of azithromycin following topical administration of a single dose of azithromycin 0.5%, 1.0%, and 1.5% eyedrops (T1225) in healthy volunteers. In: European Journal of Ophthalmology. 2008 ; Vol. 18, No. 1. pp. 13-20.
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abstract = "PURPOSE. To evaluate azithromycin tear concentrations after one drop of T1225 0.5{\%}, 1.0{\%}, and 1.5{\%} eyedrops. METHODS. In this randomized, double-masked study, 91 healthy volunteers received one drop into each eye of T1225 0.5{\%} (n=23), T1225 1.0{\%} (n=38), or T1225 1.5{\%} (n=38). Azithromycin tear concentrations were measured by HPLC-MS at seven time points for 24 hours. Tolerability was evaluated. RESULTS. T1225 1.0{\%} and 1.5{\%} had similar pharmacokinetic profiles. After a post-instillation peak (167 to 178 mg/L after 10 minutes), mean concentrations remained above 7 mg/L for 24 hours (except for T1225 1{\%} at H24). A delayed increase of the azithromycin mean tear concentration might be explained by the known late azithromycin release from tissues after storage in cells. Areas under inhibitory curve (AUICs) of T1225 1.0{\%} and 1.5{\%} were higher than AUICs of T1225 0.5{\%} and ranged between 47 and 90. The three T1225 concentrations were safe for the ocular surface. CONCLUSIONS. Once daily instillation of T1225 1.0{\%} and 1.5{\%} was shown to reach an AUIC markedly above the required threshold for an antibacterial activity against Gram-positive bacteria (25-35). These results suggest that a BID instillation is more likely to ensure antimicrobial activity against Gram-negative bacteria (threshold >100).",
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AU - Garraffo, R.

AU - Elena, P. P.

AU - Pouliquen, P.

AU - Delval, L.

AU - Rigal, D.

AU - Dubray, C.

AU - Goldschmidt, P.

AU - Tabbara, K.

AU - Cochereau, I.

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N2 - PURPOSE. To evaluate azithromycin tear concentrations after one drop of T1225 0.5%, 1.0%, and 1.5% eyedrops. METHODS. In this randomized, double-masked study, 91 healthy volunteers received one drop into each eye of T1225 0.5% (n=23), T1225 1.0% (n=38), or T1225 1.5% (n=38). Azithromycin tear concentrations were measured by HPLC-MS at seven time points for 24 hours. Tolerability was evaluated. RESULTS. T1225 1.0% and 1.5% had similar pharmacokinetic profiles. After a post-instillation peak (167 to 178 mg/L after 10 minutes), mean concentrations remained above 7 mg/L for 24 hours (except for T1225 1% at H24). A delayed increase of the azithromycin mean tear concentration might be explained by the known late azithromycin release from tissues after storage in cells. Areas under inhibitory curve (AUICs) of T1225 1.0% and 1.5% were higher than AUICs of T1225 0.5% and ranged between 47 and 90. The three T1225 concentrations were safe for the ocular surface. CONCLUSIONS. Once daily instillation of T1225 1.0% and 1.5% was shown to reach an AUIC markedly above the required threshold for an antibacterial activity against Gram-positive bacteria (25-35). These results suggest that a BID instillation is more likely to ensure antimicrobial activity against Gram-negative bacteria (threshold >100).

AB - PURPOSE. To evaluate azithromycin tear concentrations after one drop of T1225 0.5%, 1.0%, and 1.5% eyedrops. METHODS. In this randomized, double-masked study, 91 healthy volunteers received one drop into each eye of T1225 0.5% (n=23), T1225 1.0% (n=38), or T1225 1.5% (n=38). Azithromycin tear concentrations were measured by HPLC-MS at seven time points for 24 hours. Tolerability was evaluated. RESULTS. T1225 1.0% and 1.5% had similar pharmacokinetic profiles. After a post-instillation peak (167 to 178 mg/L after 10 minutes), mean concentrations remained above 7 mg/L for 24 hours (except for T1225 1% at H24). A delayed increase of the azithromycin mean tear concentration might be explained by the known late azithromycin release from tissues after storage in cells. Areas under inhibitory curve (AUICs) of T1225 1.0% and 1.5% were higher than AUICs of T1225 0.5% and ranged between 47 and 90. The three T1225 concentrations were safe for the ocular surface. CONCLUSIONS. Once daily instillation of T1225 1.0% and 1.5% was shown to reach an AUIC markedly above the required threshold for an antibacterial activity against Gram-positive bacteria (25-35). These results suggest that a BID instillation is more likely to ensure antimicrobial activity against Gram-negative bacteria (threshold >100).

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KW - Minimal inhibitory concentration (MIC)

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KW - Tear pharmacokinetics/pharmacodynamics

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