The medical, social, and economic consequences of drug overdose make the obtainment of safe and effective methods for the accelerated removal of drug from the body a necessity. Phenobarbital is the 5th most abused prescription drug in the USA (1983); the effects of overdose last for days due to the drug's long half-life. Administration of activated charcoal is recommended for both the acute ingestion of and systemic absorption of phenobarbital. Minimal work has been done to characterize the actual process of drug adsorption onto activated charcoal. Most experiments utilize a Langmuir treatment without verification of isotherm type. Differences in adsorption effectiveness have been attributed to changing surface area and average pore size; these characteristics do not solely determine the adsorption behavior of a drug on an adsorbent. The effects of surface composition of activated charcoal on the adsorbent. The effects of surface composition of activated charcoal on the adsorption of a given drug need to be studied. Activated charcoal poses problems; it is gritty and causes constipation. To eliminate these problems, suspending agents, flavors and alternate adsorbents have been used. In this proposal, effects of sorbitol (a sweetner and dispersing aid) and a nonionic polystyrene resin are of interest. Sorbitol has both improved and diminished drug adsorption. Polystyrene resin has been condemned for reaching equilibrium too slowly, a problem for which it would seem that both a logical explanation and ready solution exist. The proposal is divided into two parts: in vitro and in vivo. Comparison of the mechanism and thermodynamics of the adsorption of phenobarbital onto various adsorbents plus the evaluation of sorbitol effects will be done by established physical-chemical methods of surface analysis. The clinical studies will characterize the drug-adsorbent interaction in the gastrointestinal tract between phenobarbital (200mg) and 3 charcoal preparations (2 flavored with sorbitol). Each charcoal (30gm) studied will have 14 healthy male volunteers participating in 4 treatments: a) I-oral phenobarbital without charcoal; d) II-oral phenobarbital with charcoal; c) III-intravenous phenobarbital without charcoal; d) IV-intravenous phenobarbital with charcoal. Serum phenobarbital levels will be measured by EMIT. This data will be correlated with the data from the extensive in vitro work for charcoal. The correlations between the in vitro and in vivo data will be used to develop predictive relationships. The data will demonstrate the most effective charcoal preparation for accelerating the elimination of phenobarbital. More importantly, the predictive relationships will provide the basis for the manufacture of better charcoals.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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University of Iowa
Schools of Pharmacy
Iowa City
United States
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