Characterization of secretory intestinal transport of phenolsulfonphthalein.
It is known that secretory transport limits the oral bioavailability of certain drugs. However, there is little information on the secretion of anionic compounds in the intestine. Phenolsulfonphthalein (PSP) and p-aminohippuric acid (PAH) have been used widely as substrates for organic anion transport systems. PAH is transported in the secretory direction in the intestine. It is possible that PSP and PAH share the same transport system at the mucosal membrane. The purpose of this study was to characterize the transport system for PSP in the intestine. In the jejunum, the serosal-to-mucosal permeation rate of PSP was significantly reduced in an ATP-depleted condition, whereas a significant difference was not observed in the ileum. Some multidrug resistance-associated protein 2 (Mrp2) inhibitors inhibited PSP permeation in the jejunum. However, pravastatin, a substrate of Mrp2, did not inhibit the PSP permeation. The jejunal secretory transport of pravastatin was significantly reduced in an ATP-depleted condition and by addition of probenecid, but PSP did not affect the jejunal permeation of pravastatin. These results suggest that PSP is secreted into the intestinal lumen by Mrp2-like transporter and that two Mrp2 substrates, PSP and pravastatin, are likely to be transported by different transport systems at the mucosal membrane.
Itagaki
Shirou
S
Department of Clinical Pharmaceutics & Therapeutics, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Chiba
Makoto
M
Shimamoto
Soji
S
Sugawara
Mitsuru
M
Kobayashi
Michiya
M
Miyazaki
Katsumi
K
Hirano
Takeshi
T
Iseki
Ken
K
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D007213:Indomethacin / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D007700:Kinetics; D008297:Male; D010539:Permeability; D010637:Phenolsulfonphthalein / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011339:Probenecid / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D010130:p-Aminohippuric Acid / Q000494:pharmacology
D000255:Adenosine Triphosphate; D010637:Phenolsulfonphthalein; D011339:Probenecid; D007213:Indomethacin; D010130:p-Aminohippuric Acid