PT  - JOURNAL ARTICLE
AU  - W B Van de Graaff
AU  - W L Thompson
AU  - I Sunshine
AU  - D Fretthold
AU  - F Leickly
AU  - H Dayton
TI  - Adsorbent and cathartic inhibition of enteral drug absorption.
DP  - 1982 Jun 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 656--663
VI  - 221
IP  - 3
4099  - http://jpet.aspetjournals.org/content/221/3/656.short
4100  - http://jpet.aspetjournals.org/content/221/3/656.full
SO  - J Pharmacol Exp Ther1982 Jun 01; 221
AB  - 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.