TY - JOUR
T1 - 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
AU - Chiambaretta, Frédéric
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.
PY - 2008/1
Y1 - 2008/1
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).
KW - Area under the inhibitory curve (AUIC)
KW - Azithromycin eyedrops
KW - Minimal inhibitory concentration (MIC)
KW - T1225
KW - Tear pharmacokinetics/pharmacodynamics
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M3 - Article
C2 - 18203079
AN - SCOPUS:41149096153
SN - 1120-6721
VL - 18
SP - 13
EP - 20
JO - European Journal of Ophthalmology
JF - European Journal of Ophthalmology
IS - 1
ER -