[Effects of Chinese herbal medicines on intestinal drug absorption].
Sho-saiko-to (Xiao-Chai-Hu-Tang), one of the major traditional Chinese medicines, has been frequently prescribed with other synthetic or biotechnological drugs for the treatment of various acute or chronic diseases in Japan, and thus it is important to understand the interactions between Sho-saiko-to and coadministered drugs. This paper reviews the effects of Sho-saiko-to on the pharmacokinetics and pharmacodynamics of concomitant drugs in the gastrointestinal tract. Sho-saiko-to slightly hastens the gastrointestinal absorption of the sulfonylurea compound tolbutamide. Furthermore, it is considered that the increase in the gastrointestinal absorption rate by Sho-saiko-to may potentiate the hypoglycemic effects of tolbutamide in the early period after oral administration. Sho-saiko-to can facilitate the epithelial membrane permeability of tolbutamide at an early phase across the rat jejunum in situ and Caco-2 cell monolayers. It is also suggested that Sho-saiko-to enhances the energy-dependent transport of tolbutamide and has an inhibitory effect on the passive paracellular transport of tolbutamide in Caco-2 cells. This result might be related to the accelerated in vivo absorption rate of tolbutamide by concomitant dosing with Sho-saiko-to in rats. In addition, Sho-saiko-to has inhibitory effects on the efflux pump mediated by MDR1, and it appears that the crude constituents in Glycyrrhizae radix, glycyrrhizic acid and liquiritin, contribute to MDR1 suppression.
Nishimura
Nobuhiro
N
Department of Pharmacy, Shimane University Hospital, Izumo 693-8501, Japan. nnishi@med.shimane-u.ac.jp
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors; D000818:Animals; D018938:Caco-2 Cells / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics*; D007408:Intestinal Absorption / Q000187:drug effects*; D007583:Jejunum / Q000378:metabolism; D051381:Rats; D013453:Sulfonylurea Compounds / Q000493:pharmacokinetics*; D014044:Tolbutamide / Q000493:pharmacokinetics*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004365:Drugs, Chinese Herbal; D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; C461320:shosaiko-to; D014044:Tolbutamide