Figure 7.10 Absorption%> versus PAMPA flux [547]: (a) pH 6.5; (b) pH 7.4. [Reprinted from Kansy, M.; Senner, F.; Gubernator, K. J. Med. Chem., 41, 1070-1110 (1998), with permission from the American Chemical Society.]

screening [48,82,91,97,108-110,510-515,551-553]. The outliers in their assays, inset in Fig. 7.10, were molecules known to be actively transported. Since the artificial membranes have no active transport systems and no metabolizing enzymes, the assay would not be expected to model actively transported molecules. What one sees with PAMPA is pure passive diffusion, principally of the uncharged species.

More recently, several publications have emerged, describing PAMPA-like systems. [25-28,509, 554-565] The PAMPA method has attracted a lot of favorable attention, and has spurred the development of a commercial instrument, [25-28,556] and the organization of the first international symposium on PAMPA in 2002 [565].

7.3.2 Hexadecane PAMPA Model (Novartis Model)

Faller and Wohnsland [509,554] developed the PAMPA assay using phospholipid-free hexadecane, supported on 10-p.m thick polycarbonate filters(20% porosity,

0 0

Post a comment