Change in tolbutamide permeability in rat jejunum and Caco-2 cells by Sho-saiko-to (Xiao Chai Hu Tang), a Chinese traditional medicine.
OBJECTIVE
This study was designed to investigate the effects of Sho-saiko-to (Xiao Chai Hu Tang), a Chinese traditional medicine, on the membrane permeability of tolbutamide in the intestinal tract. We carried out an in-situ loop study with rat jejunum and a transport study with Caco-2 cell monolayers.


METHODS
In the in-situ loop study, absorption clearance of tolbutamide was estimated from the drug concentrations in the loop and plasma. The apical-to-basolateral and basolateral-to-apical transport of tolbutamide and d-mannitol, a paracellular transport marker, was assessed using Caco-2 cell monolayers cultured on a polycarbonate membrane.


RESULTS
The absorption clearance of tolbutamide was enhanced by a concomitant dose of Sho-saiko-to over 10 min in the rat in-situ loop. Sho-saiko-to increased the apical-to-basolateral transport of tolbutamide, whereas the basolateral-to-apical transport of this drug was reduced by Sho-saiko-to. On the other hand, in both directions the P(app) of d-mannitol was reduced by the presence of Sho-saiko-to. Furthermore, the apical-to-basolateral transport of tolbutamide in ATP-depleted Caco-2 cells was diminished by Sho-saiko-to. These findings suggest that Sho-saiko-to can facilitate the epithelial membrane permeability of tolbutamide across the rat jejunum in-situ and Caco-2 cell monolayers. Since Sho-saiko-to suppressed the passive transport of tolbutamide from the apical-to-basolateral side, enhanced permeability may be related to effects of Sho-saiko-to on the energy-dependent transport of tolbutamide in the intestine.


CONCLUSIONS
Our findings suggest that Sho-saiko-to might facilitate the energy-dependent transport of tolbutamide across the rat jejunum in-situ and Caco-2 cell monolayers.
Nishimura
Nobuhiro
N
Department of Pharmacy, Shimane University Hospital, Shimane, Japan.
Uemura
Tomichika
T
Iwamoto
Kikuo
K
Naora
Kohji
K
D000818:Animals; D001693:Biological Transport, Active; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability / Q000187:drug effects*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D041743:Herb-Drug Interactions; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D007583:Jejunum / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008353:Mannitol / Q000378:metabolism; D008516:Medicine, Chinese Traditional; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014044:Tolbutamide / Q000493:pharmacokinetics*
D004365:Drugs, Chinese Herbal; C461320:shosaiko-to; D008353:Mannitol; D014044:Tolbutamide