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a 5-(3-Dimethylaminomethyl-4-hydroxy-phenylsulfonyl) thiophene-2-sulfonamide.

a 5-(3-Dimethylaminomethyl-4-hydroxy-phenylsulfonyl) thiophene-2-sulfonamide.

times to maximal aqueous humor concentration (Tmax) for various drugs. Tmax falls within a range of 10 minutes to 2 hours.

As mentioned, the typical percentage of drug absorbed into the eye following a topical ocular dose is in the range of 1-10%, while systemic bioavailability can be as high as 100% (Table 2). For calculating bioavailability fraction (F), aqueous humor AUC can be determined by intracam-eral injection (27,46) or topical instillation with plugged drainage ducts (28). In the former case, aqueous humor AUCs, normalized for dose, are compared between topical and intracameral doses to derive F. In the latter case, Patton and Robinson (28) calculated F using the following equation:

where D is the instilled dose, k10 is the loss of drug from the precorneal area, and V is the estimated aqueous humor volume of 0.3 mL.

For some drugs, such as topical anti-infectives, tear bioavailability and not aqueous humor bioavailability is the determining pharmacokinetic factor for efficacy. Unlike aqueous humor, tear film is readily sampled in humans. Depending on the method of collection, analytical sensitivity may be a limiting factor due to small volumes typically collected and the short precorneal residence time typically encountered. Nevertheless, when area under the tear concentration-time curve values are available, bioavailabilities can be calculated and compared between formulations. Tear sampling technique may be an important factor in obtaining this type of data. For example, Ding et al. compared two tear sampling techniques (capillary tubes and Schirmer strips) and one recovery technique (cotton swabs) for suitability for determining precorneal drug levels as a function of time for ophthalmic gels (47). All three methods yielded similar corneal contact times (about 1 hour). Capillary tubes proved effective for tear sampling, while the strip method suffered from gel carry-over. The cotton swab technique was gentle, easy, and nondestructive and yielded recovery of total drug in the cul-de-sac, but failed to provide information for tear film.

2. Ocular Distribution

Compared to absorption and elimination, distribution is generally more difficult to describe kinetically. In the concentration-time curve shown in Figure 4, distribution is associated with the log-linear decline in aqueous humor concentration immediately following peak concentration and before the terminal elimination phase.

a. Distribution Within the Anterior Segment. The fundamental parameter to describe distribution is volume of distribution (Vd), which is de-

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