Study on transport of disopyramide into the intestinal lumen aimed at gastrointestinal dialysis by activated charcoal in rats.
The characteristics of exsorption and/or excretion of disopyramide into the gastrointestinal lumen have been investigated after intravenous administration of the drug at doses of 10 and 30 mg kg-1 to rats by the in-situ single pass perfusion technique. Disopyramide was appreciably excreted into the bile where its levels were approximately ten-fold higher than those in the serum. The exsorption rate of disopyramide and mono-N-dealkyldisopyramide (MND) into the perfusate was increased with an increase in the serum level following an increase from 10 to 30 mg kg-1 in the dose of disopyramide. The average amounts of disopyramide exsorbed into the perfusate were 17.0 and 18.4% at the dose of 10 and 30 mg kg-1, respectively, whereas those of MND were less than 1% at both doses of disopyramide. Oral administration of activated charcoal reduced the serum disopyramide levels after intravenous administration of the drug (20 mg kg-1) compared with the control treatment. By oral administration of activated charcoal, t 1/2 and AUC were decreased to 89 and 82%, respectively, and Cltot was increased to 122% compared with the corresponding control treatment. Vd was not different between the treated rats and control rats. These results suggest that the oral administration of activated charcoal can enhance the clearance of disopyramide and MND from the blood.
Arimori
K
K
Department of Pharmacy, Kumamoto University Hospital, Japan.
Nakano
M
M
D000284:Administration, Oral; D000327:Adsorption; D000818:Animals; D001646:Bile / Q000378:metabolism; D002606:Charcoal / Q000008:administration & dosage / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003956:Dialysis; D004064:Digestive System / Q000187:drug effects / Q000378:metabolism*; D004206:Disopyramide / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics*; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014551:Urinary Tract / Q000378:metabolism
D002606:Charcoal; C030438:4-(isopropylamino)-2-(2-pyridyl)-2-phenylbutyramide; D004206:Disopyramide