Transient analysis of ocular drug delivery: zero-volume effect.

Dose volume reduction is one method for reducing the nonproductive loss of ophthalmic drugs caused by premature drainage from the precorneal area. A new mathematical method is presented for calculating the bioavailability enhancement achieved by the dose volume reduction method. This new model suggests that the steady-state assumption used in a previous paper overestimated the bioavailability enhancement, depending upon physical factors such as distribution and diffusion coefficients of the drug in tissue and solution. The analysis shows that transient effects can make a difference up to a complete elimination of the zero-volume effect in those cases where the distribution coefficient is large and the permeability coefficient is small (i.e., for large, lipophilic molecules).