Values in parentheses indicate the time (hours) to reach the peak concentrations. a The half-life noted in these studies is not the terminal phase half-life, but rather the time required for the average concentration in the vitreous to drop by a factor of 2 immediately following injection. The terminal phase half-life would not be expected to change with changes in injection position since the terminal phase occurs after a pseudo equilibrium has been achieved in the vitreous. After this point only vitreous diffusivity and retinal permeability would govern the rate of elimination. b Peak concentration in vitreous adjacent hyaloid opposite the location of the intravitreal injection.
Cmean in vitreous trends were noted when comparing the half-life of fluorescein in the phakic versus aphakic eye model. In both cases, the longest half-life was found for a central injection and the shortest half-life was found for a hyaloid-displaced injection. The half-life for the lens-displaced injection, however, was much lower in the aphakic eye model than in the phakic eye model. Placing the injected drug closer to the lens capsule in the aphakic eye model would initially produce a rapid loss of drug to the posterior chamber of the aqueous humor. However, in the phakic eye model, since there is no loss across the lens, injecting the drug closer to the lens has little effect. The initial drug loss across the lens capsule in the aphakic eye model is confirmed by comparing, in the aphakic and phakic eye models, the ratio between the mean concentrations at 4 and 24 hours for the central and lens-displaced injections. In the aphakic eye model, the mean concentration 4 hours following a central injection is 1.75 times greater than the mean concentration from a lens-displaced injection; this ratio increases slightly at 24 hours. In the phakic eye model, however, this ratio is only approximately 1.02, despite the fact that the mean concentration in the vitreous is the same for the phakic and aphakic eye models 4 hours following a central injection. The higher ratio in the aphakic eye model is therefore due to increased transport across the lens capsule, much of which occurs within the first 4 hours following an injection.
The mean vitreous concentrations in the phakic and aphakic eye models differ by less than 10% following central, retinal-displaced, and hyaloid-displaced injections, regardless of the sample time considered. However, the peak concentrations of fluorescein adjacent to the lens and retina were higher in the phakic eye model than in aphakic eye model for all the injection positions. Adjacent to the lens, the peak concentrations were higher in the phakic eye model because there is no loss across the lens. Adjacent to the retina, the peak fluorescein concentrations were only significantly higher in the phakic eye model for the central and lens-displaced injections. This is due to increased loss across the lens capsule in the aphakic eye model and the fact that the distance between the injection site and the recording site is slightly larger in the aphakic eye model than in the phakic eye model. The peak concentrations adjacent to the hyaloid membrane were higher in the aphakic eye model than in the phakic eye model for the central and lens-displaced injections. This is due to the fact that, in the aphakic eye model, the injection sites are slightly closer to the site adjacent to the hyaloid where the concentrations were recorded.
Figure 16 shows the model calculated concentration profile of fluorescein glucuronide in half of a cross section of the vitreous 36 hours after a central injection in the phakic and aphakic eye models. In this case, since fluorescein glucuronide has a low retinal permeability and is eliminated primarily across the hyaloid membrane, the concentration contours are perpendicular to the surface of the retina. Table 7 lists the half-lives, mean concentrations, and peak concentrations of fluorescein glucuronide within the vitreous as a function of injection position for both the phakic
and aphakic eye models. It should be noted that the different half-lives reported in Table 6 or Table 7, with respect to injection position, are due to differences in elimination rates immediately following the injection that depend upon the injection position.
Table 7 Half-Life and Peak and Mean Vitreous Concentrations of Fluorescein Calculated Using the Aphakic and Phakic Eye Models Following Intravitreal Injections at Different Locations
Cpeak in vitreous
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