Histological image of the rectal crypts (transverse section).

<p>Regular spacing of the crypt openings is seen. Reprinted from <a href="http://www.lab.anhb.uwa.edu.au/mb140/" target="_blank">http://www.lab.anhb.uwa.edu.au/mb140/</a> [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0167696#pone.0167696.ref025" target="_blank">25</a>].</p

Average concentrations in different compartments vs. time.

<p>Standard conditions for gel, epithelial and stromal thicknesses. These are spatial averages through the depths of the compartments. The simulated biopsy is the spatial average of combined epithelial and stromal compartments.</p

TFV concentration profile versus depth of the stroma.

<p>This is after 5 minutes of enema retention for a small, open crypt. Different times are indicated by different colors (cf. color bar), and the flattening of the concentration profile vs. depth with increasing time is clearly seen.</p

Summary pharmacokinetic parameters from computations by model for single application of 4.

<p>Values in parentheses and italics are corresponding human data for biopsy and blood compartments from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0074404#pone-0074404-t003" target="_blank">Table 3</a> of Schwartz et al (2011).</p

Volume average TFV concentrations vs. time in the compartments for varying advective flow.

<p>This is contrasted to a closed crypt (solid lines; see text for further details). Enema retention time is 5 minutes, and crypt size is small. Effects of advection on concentrations are relatively small (see text).</p

Summary pharmacokinetic parameters in the epithelium and stroma with varying epithelial thickness (h_e).

<p>Summary pharmacokinetic parameters in the epithelium and stroma with varying epithelial thickness (h_e).</p

Results for TFV concentrations in a simulated biopsy.

<p>The biopsy contains both epithelium and some stromal tissue (see text). Enema retention time is 5 (blue lines), 10 (green lines) or 20 (red lines) min. Crypts are either open (hatched lines) or closed (solid lines). Biopsy thickness is either 1 mm (left y-axis) or 3 mm (right y-axis), and crypt size is small.</p

Results for TFV-DP concentrations in a simulated biopsy.

<p>The biopsy contains both epithelium and some stromal tissue (see text). Enema retention time is 5 min (blue lines), 10 (green lines) or 20 (red lines) min. Crypts are either open (hatched lines) or closed (solid lines). Biopsy thickness is either 1 mm (left y-axis) or 3 mm (right y-axis), and crypt size is small.</p

Volume-averaged TFV and TFV-DP concentrations vs. time after enema application in different compartments.

<p>Enema retention times are 5, 10, or 20 minutes (blue, green and red lines). A small sized crypt is contrasted between being open (hatched line) or closed to the luminal enema fluid (see further details in text). Results are also shown for compartmental volume-averaged concentrations vs. time, as computed for the earlier vaginal model for a tenofovir gel[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0167696#pone.0167696.ref020" target="_blank">20</a>]; here there is also complete vehicle coating along the canal. Both vehicles initially contain 10⁷ ng/mL (1%) TFV. Note the much lower and slower developing concentrations in the vaginal mucosal tissue. Contrasts in rectal stromal TFV and TFV-DP concentrations for open vs. closed crypts are also evident.</p

Percentage of stromal volume containing prophylactic TFV-DP concentration vs time.

<p>This is termed “percent protected” after 1 minute or 5 minutes of enema retention for a small crypt. See text for specification of “protected.” Contrasts between the shorter and longer retention times, as well as open vs. closed crypt status, are clearly seen.</p