Efficacy and toxicity of the solvent polyethylene glycol 400 in monkey model

Abstract

Several antiepileptic drugs, such as carbamazepine and clonazepam, have low bioavailability in solid form and are insoluble in an aqueous solution. Alcohol solvents are often employed as vehicles when these drugs are studied in animal models. Secondary and particularly tertiary alcohols are suspected of some anticonvulsant activity. The present research evaluated the possibility that polyethylene glycol 400 (PEG 400) might be efficacious, toxic, or both. Monkeys (N = 11) rendered epileptic by aluminum-hydroxide were administered PEG 400 by constant rate (1 ml/hr) intravenous infusion for 3--4 weeks, preceded and followed by several weeks of baseline. At a concentration of 60%, PEG 400 significantly reduced seizure frequency, but also exhibited severe side effects. These findings suggest that experimental testing of anticonvulsants may be compromised when this or similar solvents are used chronically.