The study on the biological fate of paraben at the dose of practical usage in rat. II. The pharmacokinetic study on the blood concentration after the administration of ethyl paraben or p-hydroxybenzoic acid.

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Abstract
The biological fates of the preservatives ethyl paraben (ethyl p-hydroxybenzoate) or p-hydroxybenzoic acid (HB), and p-hydroxybenzoic acid in rat were investigated after i.v. and intraduodenal administrations at a dose of 2 mg/kg. The blood concentrations were measured in detail 3 min after the administration and at appropriate time intervals until 90 min. Areas under the blood concentration curves and clearances were calculated from these time course data. Ethyl paraben was little detected in blood after intraduodenal administration. The intestinal metabolism and the 1st pass effect in liver contribute to the hydrolysis of ethyl paraben. Total radioactivity after intraduodenal administration did not show the maximum peak and decreased rapidly. The maximum peak was not observed in the time course of p-hydroxyhippuric acid after i.v. administration. The rate of hydrolysis, absorption and conjugation were very rapid. The differences of the areas under the blood concentration curves of p-hydroxybenzoic acid or p-hydroxyhippuric acid were between the routes or chemical forms of administration. Complex kinetic mechanisms were assumed in the biological fates of these compounds as follows: Conjugation to p-hydroxyhippuric acid is better in ethyl paraben administration than p-hydroxybenzoic acid and in intraduodenal administration than i.v. administration. These phenomenon cannot be explained by the conventional kinetic model which is constructed with the connected blood compartments in series. The kinetic models including the assumed routes directly conjugating ethyl paraben in blood or intestine to p-hydroxyhippuric acid were presented and the least square curve fitting analyses carried out on these kinetic models.