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Studies on the toxicokinetics of intragastricallyadministered paracetamol, aminophenazone, caffeine and chlorphenamine maleate tablets in rats
Abstract
Purpose: To study the toxicokinetics of paracetamol (PCT), aminophenazone (ACP), caffeine (CFN) and chlorphenamine maleate (CPM) tablets after a single oral gavage, and after oral gavage for 14 consecutive days in rats.
Methods: Eighty Sprague Dawley (SD) rats (half male, half female) were randomly divided into 4 groups with 20 rats in each group. Half of the rats were used for the toxicokinetic test after a single oral gavage of PCT, ACP, CFN and CPM tablets, while rats in the other half were used for the toxicokinetic tests after oral gavage for 14 consecutive days. The doses of the four groups were set as 0, 0.5, 1 and 2 tablets/kg body weight, respectively. Blood was taken from the rats and the plasma concentration of paracetamol was determined.
Results: There was a significant difference in AUC0-∞ between male and female rats at single oral gavage of 2 tablets/kg of each of the drugs. The exposure amount of PCT (AUC0~t, AUC0-∞ and Cmax) increased with increase in dose, and showed a good linear relationship after a single intragastric administration of each drug, and after 14 consecutive days of intragastric administration at low, medium and high doses.
Conclusion: The amount of PCT to which SD rats are exposed after a single intragastric administration of PCT, ACP, CFN and CPM tablets is lower in male than in female rats. However, no significant gender difference in exposure results when these drugs are given intragastrically for 14 consecutive days.
