Adsorbent and cathartic inhibition of enteral drug absorption.

The effects on absorption of drugs given by mouth of adsorbents (charcoals and resins) and cathartics (osmotic and oil) were studied in vitro and in vivo using acetaminophen (paracetamol) as a test drug. In vitro adsorption isotherms were measured at 37 degrees C in simulated gastric and gastric plus intestinal juices. Maximum binding capacity (MBC) of 16 charcoals and resins varied 30-fold, from 0.36 to 9.32 mol/kg. Dissociation constants varied directly with MBC. In vitro adsorption was little changed by addition of d-mannitol and d-sorbitol, N-acetylcysteine (NAC) or l-methionine. Acetaminophen (0.6 g/kg by orogastric tube) was given to 17 dogs protected by i.v. injections of NAC and methylene blue. One minute later, dogs were given: 1) water; 2) Norit A or Nuchar 1110 charcoal, 3 g/kg; 3) d-mannitol and d-sorbitol, 2 g/kg or castor oil, 3 ml/kg; or 4) both charcoal and either d-mannitol and d-sorbitol or castor oil. Cathartics alone decreased the area under plasma acetaminophen concentrations 15 to 30%. Charcoals alone reduced the area under plasma acetaminophen concentration 93%. Each cathartic diminished the charcoal inhibition of acetaminophen absorption. In mice given acetaminophen by orgastric tube, the acute lethality was decreased more by a new petroleum-based charcoal than by standard wood-based charcoals. Reduction of acetaminophen lethality in mice paralleled the in vitro MBC of adsorbents. Charcoals did not avidly adsorb l-methionine or NAC in vitro. Charcoal did not decrease the l-methionine or NAC protection of acetaminophen-poisoned mice. Charcoals with large MBC diminish absorption and lethality of acetaminophen taken by mouth; cathartics have little effect on acetaminophen absorption.