Figure 13 Log-linear plot of pupillary response (miotic or mydriasis) versus time. Dotted line indicates absorption phase after stripping off elimination phase. (Reprinted with permission from Maurice, D. M., and Mishima, S. (1984). Ocular pharmacokinetics. In: Pharmacology of the Eye. (M. L. Sears, ed.), Springer-Verlag, Berlin, p. 56.) (Ref. 4).

response and concentration of phenylephrine in the iris was developed and expressed as follows:

where AE(t) is the difference between pupillary diameter before and after drug instillation at time t, K'm is the drug concentration in the iris at half maximal mydriatic response (one-half AEmax), and Ca(t) is the concentration of drug in aqueous humor at time t. In the case of tolerance, K'm is no longer constant but changes with time and can be calculated for each time interval as:

A plot of K'm(t) versus time was linear up to 90 minutes but increased thereafter through 240 minutes postinstillation verifying the development of tolerance (114)

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