Date of Award

1980

Degree Type

Thesis

Degree Name

Master of Science in Pharmacology and Toxicology

Department

Pharmacology and Toxicology

First Advisor

George C. Fuller

Abstract

A liquid membrane system was investigated as a potential antidotal treatment for acute drug overdose. The effectiveness of orally administered liquid membranes in simulated acute secobarbital, phencyclidine and strychnine poisoning was assessed in fasting rats. Four milliliters of a liquid membrane suspension was administered immediately following drug intubations. The effect of liquid membrane on gastrointestinal absorption of secobarbital and phencyclidine was determined by comparison of duration of action (sleeping time) and blood drug concentration over time in drug controls and treated rats. The effect on phencyclidine absorption was also determined from the total amount of drug and metabolites excreted in the urine over twenty-four hours. The effectiveness of liquid membranes and activated charcoal for reducing strychnine absorption was assessed by acute toxicity experiments. Duration of action of phencyclidine was 22 percent longer in liquid membrane treated rats while no significant difference existed between groups in secobarbital sleeping times. Blood level versus time analysis revealed no differences in blood levels between control and treated groups in both secobarbital and phencyclidine experiments. No difference existed in the total recovery of phencyclidine in urine in control and treated groups. Liquid membranes failed to protect rats from strychnine induced toxicity, whereas activated charcoal completely inhibited the toxic effect. These studies show that liquid membranes are relatively ineffective in reducing drug absorption in vivo and that the system probably serves as a reservoir for sustained release of the drug as it passes through the gastrointestinal tract. The lack of in vivo efficacy may be attributed to an appreciable reduction in liquid membrane stability in the presence of gastrointestinal constituents such as bile salts and pancreatic secretions.

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