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Figure 9 Concentration of fluorescein at the vitreous site adjacent to the retina following 15 mL injections at four different vitreous locations. Peak concentrations of fluorescein at this vitreous site varied by up to three orders of magnitude, depending on the initial injection position. Similar variations were noted for the other sites within the vitreous where the concentrations were monitored.

eous site adjacent to the lens varied by up to two orders of magnitude, depending on the location of the injection (Table 2). Similar variations were also noted for fluorescein glucuronide; peak concentrations produced by the different injection sites varied by up to two orders of magnitude at the different vitreous sites (Table 3).

It is also important to note that there were significant variations in the model calculated peak concentrations at each vitreous site produced by an individual injection location. For example, for the hyaloid-displaced injection, the peak concentration next to the injection (adjacent hyaloid) was over three orders of magnitude higher than the peak concentration next to the hyaloid membrane opposite the injection location (Table 3). Furthermore, the time to reach the maximum fluorescein concentration varied from approximately 6 minutes to 12 hours, depending upon the proximity of the monitoring site to the injection site. Similarly, the time to reach the peak concentration of fluorescein glucuronide ranged from approximately 10 minutes to 24 hours. The variations observed for the AUC-time curve followed

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Time (hours)

Figure 9 Concentration of fluorescein at the vitreous site adjacent to the retina following 15 mL injections at four different vitreous locations. Peak concentrations of fluorescein at this vitreous site varied by up to three orders of magnitude, depending on the initial injection position. Similar variations were noted for the other sites within the vitreous where the concentrations were monitored.

Figure 10 Concentration of fluorescein glucuronide at the vitreous site adjacent to the retina following 15 mL injections at four different vitreous locations. Peak concentrations of fluorescein glucuronide varied by up to three orders of magnitude at this site within the vitreous, depending on the initial position of the injection. Similar variations in concentrations were noted for the other sites within the vitreous.

Figure 10 Concentration of fluorescein glucuronide at the vitreous site adjacent to the retina following 15 mL injections at four different vitreous locations. Peak concentrations of fluorescein glucuronide varied by up to three orders of magnitude at this site within the vitreous, depending on the initial position of the injection. Similar variations in concentrations were noted for the other sites within the vitreous.

trends similar to those observed for the peak concentration values. For fluorescein, AUC values for a specific vitreous site varied by over two orders of magnitude, depending on the location of the injection. AUC values for fluorescein glucuronide for a specific vitreous site also varied by over an order of magnitude. The AUC represents the cumulative exposure of a particular tissue to a drug over time and may therefore be related to the efficacy and/or toxicity of a drug at a particular site.

The data in Table 3 also further emphasize the importance of the injection location. After 24 hours there is one-quarter the amount of fluor-escein left in the vitreous following the 15 mL hyaloid-displaced injection compared to after the 15 mL central injection. Similarily, there is one-third the amount of fluorescein glucuronide left in the vitreous following the 15 mL hyaloid-displaced injection compared to after the 15 mL retina-displaced injection. For the larger 100 mL injections, the difference between the amount of drug remaining at 24 hours for the different injection locations

Table 2 Peak Concentrations and Area Under Curve Values at Various Vitreous Sites Following 15 mL Intravitreal Injections of Fluorescein at Four Different Vitreous Locations

Vitreous site where concentration was monitored

Table 2 Peak Concentrations and Area Under Curve Values at Various Vitreous Sites Following 15 mL Intravitreal Injections of Fluorescein at Four Different Vitreous Locations

Vitreous site where concentration was monitored

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