Effect of dicyclomine on intestinal absorption, disposition and biliary excretion of dexamethasone.
The effect of dicyclomine, a cholinergic blocking agent, on the in situ intestinal absorption, plasma clearance, biliary excretion of dexamethasone was examined in rats. The plasma concentrations and area under the plasma concentration-time curve (AUC) of dexamethasone after both a single and repeated oral coadministration with dexamethasone phosphate (4 mg/kg) and dicyclomine (4 mg/kg) were significantly reduced compared with those after dexamethasone alone, without the alteration of elimination rate. The in situ absorption study also indicated that the absorption of dexamethasone was reduced to about a half after repeated coadministration of the two drugs. The renal plasma flow (RPF) in coadministration group was significantly enhanced compared with that of dexamethasone alone. The biliary excretion of dexamethasone was reduced, in proportion to the plasma concentrations, by dicyclomine. Therefore, dicyclomine should be administered taking much care in the corticosteroid treatment, because of producing the decrease in absorption.
D000284:Administration, Oral; D000818:Animals; D001646:Bile / Q000378:metabolism*; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D003907:Dexamethasone / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D004025:Dicyclomine / Q000008:administration & dosage / Q000494:pharmacology*; D004347:Drug Interactions; D007208:Indocyanine Green; D007275:Injections, Intravenous; D007408:Intestinal Absorption / Q000187:drug effects*; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D051381:Rats; D010130:p-Aminohippuric Acid / Q000378:metabolism
D003509:Cyclohexanecarboxylic Acids; D004025:Dicyclomine; D003907:Dexamethasone; D007208:Indocyanine Green; D010130:p-Aminohippuric Acid