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 OF p-HYDROXYBENZOIC ACID
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概要
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The biological fates of ethyl paraben and p-hydroxybenzoic acid in rat were investigated after intravenous and intraduodenal administrations at the dose of 2 mg/kg. The blood concentrations were measured in detail from 3 min after the administration 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. It is suggested that the intestinal metabolism and the first pass effect in liver greatly contribute to the hydrolysis of ethyl paraben. Total radio activity after intraduodenal administration did not show the maximum peak and decreased rapidly. The maximum peak was not observed also in the time course of p-hydroxyhippuric acid after intravenous administration. It shows that not only the rate of hydrolysis but also absorption and conjugation are very rapid. The differences of the areas under the blood concentration curves of p-hydroxybenzoic acid or p-hydroxyhippuric acid was found between the routes or chemical forms of administration. The complex kinetic mechanisms were assumed in the biological fates of these compounds as follows : Conjugation to p-hydroxyhippuric acid is excellent in ethyl paraben administration than p-hydroxybenzoic acid, and in intraduodenal administration than intravenous administration. These phenomenon can not be explained by the conventional kinetic model which is constructed with the connected blood compartments in series. The kinetic models including the assumed routes conjugating directly ethyl paraben in blood or intestine to p-hydroxyhippuric acid were presented, and the least square curve fitting analyses were carried out on these kinetic models.
- 公益社団法人日本薬学会の論文
著者
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Kiwada Hiroshi
Faculty Of Pharmaceutical Science University Of Tokyo:(present Address)faculty Of Pharmaceutical Sci
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HANANO Manabu
Faculty of Pharmaceutical Sciences, University of Tokyo
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AWAZU SHOJI
Faculty of Pharmaceutical Science, University of Tokyo
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Hanano Manabu
Faculty Of Pharmaceutical Science University Of Tokyo
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Awazu Shoji
Faculty Of Pharmaceutical Science University Of Tokyo:(present Address)tokyo College Of Pharmacy
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Kiwada Hiroshi
Faculty Of Pharmaceutical Science The University Of Tokushima
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