Abstract
The effects of thiamine deficiency on pharmacological and pharmacokinetic activities of chlorpheniramine were investigated in rats. Chlorpheniramine (5–10 mg/kg) showed a dose-dependent suppressive effect on muricide induced by thiamine deficiency. The ED 50 value for muricidal suppression at 1 hr was approximately 7.1 mg/kg (95% confidence limits, 5.4–9.3 mg/kg) after oral administration. Using a high-performance liquid chromatographic (HPLC) method, chlorpheniramine was detectable at 10 min in the blood and brain of rats. The present pharmacokinetic data suggest that chlorpheniramine can easily pass through the blood-brain barrier (B.B.B.) and enter the brain. It is stored therein and is later slowly released and excreted. In thiamine deficient rats, chlorpheniramine entered the brain in much higher concentrations than in normal and pair-fed rats, and significantly higher levels were maintained for a period of 1.5 hr. These results suggest that thiamine deficiency affects pharmacological and pharmacokinetic activities in rats, and support the view that there is a malfunction of the B.B.B. in thiamine deficient rats. These factors should be taken into consideration in clinical usage and dosage.
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