Elimination Phase

Elimination of drug from the eye is the least complicated process and can be discussed first. It occurs over the entire concentration-time profile, and as long as it is the slowest of pharmacokinetic processes, the latter log-linear phase of the drug concentration-time profile represents the elimination phase and its slope allows for the calculation of elimination half-life and the time necessary for completion of the process. For example, the half-life for elimination of foscarnet from rabbit vitreous humor is 34 hours (18) after intravitreal injection; therefore, the process is complete in 5 x 34 hours, or 170 hours. Foscarnet can be measured to a sensitivity of 4.5 mg/mL using an electrochemical detector with high-peformance liquid chromatography (HPLC) methodology (22).

In general, at least four or five time intervals should be spaced over the latter log llnear phase following the completion of distribution within the eye. For drugs with a much shorter half-life and a less sensitive assay than foscarnet, a practical limitation to measuring drug in the postdistributive

Figure 2 Sampling times and critical problems associated with measuring absorption, distribution, and elimination of an ocularly administered drug.

phase is the sensitivity of the assay, which could limit measuring the decline of the drug over three to five half-lives.

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