Instillation timing as the main determinant of aqueous humor nepafenac exposure.
4 affiliations
- 1IRCCS AOM Azienda Ospedaliera Metropolitana - Ospedale Policlinico San Martino, Genoa, Italy.
- 2Department of Experimental Medicine (DIMES), University of Genoa, Genoa, Italy.
- 3Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), University of Genoa, Genoa, Italy.
- 4Department of Internal Medicine (DIMI), Pharmacology and Toxicology Unit, University of Genoa, Genoa, Italy.
Abstract
Purpose
To evaluate aqueous humor concentrations of nepafenac following topical administration of 0.3% and 0.1% formulations, to assess the influence of timing of instillation on intraocular exposure.Methods
Aqueous humor samples collected during anterior segment surgery were analyzed. Nepafenac concentrations were quantified in 151 samples (0.3% instilled once daily: n = 73; 0.1% instilled three times daily: n = 78). Amfenac was quantified only in the nepafenac 0.3% group (n = 73), owing to the stepwise validation of the analytical method (see Limitations). Due to right-skewed distributions, concentrations were summarized as median (IQR) and geometric mean with 95% confidence intervals Mann-Whitney U test and Spearman's rank correlation coefficient were applied. Postoperative optical coherence tomography was performed at 1, 2, and 3 months to assess the occurrence of Irvine-Gass syndrome.Results
Geometric mean nepafenac concentrations were 22.13 nM (95% CI 15.85-30.91) for 0.3% and 21.73 nM (95% CI 13.29-35.53) for 0.1% (p = 0.319). Within the 0.1% group, instillation timing significantly influenced concentrations (p < 0.001), with markedly higher levels approximately 30-60 min after instillation compared with the 10-12 h subgroup. Amfenac correlated with nepafenac (ρ = 0.56, p < 0.001). No cases of clinically evident Irvine-Gass syndrome were observed.Conclusion
No cases of clinically evident Irvine-Gass syndrome were observed; however, the study was not powered or designed to assess clinical efficacy. Timing of instillation is a major determinant of aqueous humor nepafenac concentrations. Preoperative instillation shortly before surgery may optimize intraoperative drug availability and support maintenance of mydriasis. Standardized sampling is essential for robust pharmacokinetic comparisons.
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BibTeX
@article{macri2026instillation,
title = {{Instillation timing as the main determinant of aqueous humor nepafenac exposure.}},
author = {Angelo Macri and Annalisa Salis and Margherita Tarallo and Michele Iester and Gianluca Damonte and Francesca Mattioli},
journal = {Frontiers in molecular biosciences},
year = {2026},
month = oct,
doi = {10.3389/fmolb.2026.1913752},
url = {https://europepmc.org/article/MED/42898129},
note = {CC BY},
}
RIS
TY - JOUR
TI - Instillation timing as the main determinant of aqueous humor nepafenac exposure.
AU - Angelo Macri
AU - Annalisa Salis
AU - Margherita Tarallo
AU - Michele Iester
AU - Gianluca Damonte
AU - Francesca Mattioli
PY - 2026
DA - 2026/10/05
JO - Frontiers in molecular biosciences
DO - 10.3389/fmolb.2026.1913752
UR - https://europepmc.org/article/MED/42898129
AB - Purpose To evaluate aqueous humor concentrations of nepafenac following topical administration of 0.3% and 0.1% formulations, to assess the influence of timing of instillation on intraocular exposure.Methods Aqueous humor samples collected during anterior segment surgery were analyzed. Nepafenac concentrations were quantified in 151 samples (0.3% instilled once daily: n = 73; 0.1% instilled three times daily: n = 78). Amfenac was quantified only in the nepafenac 0.3% group (n = 73), owing to the stepwise validation of the analytical method (see Limitations). Due to right-skewed distributions, concentrations were summarized as median (IQR) and geometric mean with 95% confidence intervals Mann-Whitney U test and Spearman's rank correlation coefficient were applied. Postoperative optical coherence tomography was performed at 1, 2, and 3 months to assess the occurrence of Irvine-Gass syndrome.Results Geometric mean nepafenac concentrations were 22.13 nM (95% CI 15.85-30.91) for 0.3% and 21.73 nM (95% CI 13.29-35.53) for 0.1% (p = 0.319). Within the 0.1% group, instillation timing significantly influenced concentrations (p < 0.001), with markedly higher levels approximately 30-60 min after instillation compared with the 10-12 h subgroup. Amfenac correlated with nepafenac (ρ = 0.56, p < 0.001). No cases of clinically evident Irvine-Gass syndrome were observed.Conclusion No cases of clinically evident Irvine-Gass syndrome were observed; however, the study was not powered or designed to assess clinical efficacy. Timing of instillation is a major determinant of aqueous humor nepafenac concentrations. Preoperative instillation shortly before surgery may optimize intraoperative drug availability and support maintenance of mydriasis. Standardized sampling is essential for robust pharmacokinetic comparisons.
SN - 2296-889X
ER -