Pharmacokinetics of Paradol Analogues Orally Administered to Rats. 2016

Shuichi Setoguchi, and Daisuke Watase, and Nami Nagata-Akaho, and Akinori Haratake, and Kazuhisa Matsunaga, and Jiro Takata
Laboratory of Drug Design and Drug Delivery, Faculty of Pharmaceutical Sciences, Fukuoka University , 19-1 Nanakuma 8-Chome, Jonan-ku, Fukuoka, Japan 814-0180.

The kinetics parameters of paradols with different acyl chain lengths have been evaluated to determine their antiobesity site of action. Rats were orally administered olive oil containing 0-, 6-, 8-, or 12-paradol, and blood samples were collected at different time points. The concentrations of the paradols in the plasma were analyzed both with and without β-glucuronidase treatment. The area under the plasma concentration-time curve from 0 to 24 h (AUC(0-24h)) of the parent compounds decreased with increasing acyl chain length. Whereas 12-paradol showed the largest AUC(0-24h) with the longest time to reach its maximum plasma concentration of all of the compounds tested, the AUC(0-24h) values of the metabolites decreased with increasing acyl chain length. These results indicate that increasing acyl chain length leads to a decrease in the absorption of paradols via the intestinal tract, the wall of which was estimated to be their antiobesity site of action.

UI MeSH Term Description Entries
D007659 Ketones Organic compounds containing a carbonyl group Ketone
D008297 Male Males
D010636 Phenols Benzene derivatives that include one or more hydroxyl groups attached to the ring structure.
D002396 Catechols A group of 1,2-benzenediols that contain the general formula R-C6H5O2. Pyrocatechols,o-Dihydroxybenzenes,ortho-Dihydroxybenzenes,o Dihydroxybenzenes,ortho Dihydroxybenzenes
D005233 Fatty Alcohols Usually high-molecular-weight, straight-chain primary alcohols, but can also range from as few as 4 carbons, derived from natural fats and oils, including lauryl, stearyl, oleyl, and linoleyl alcohols. They are used in pharmaceuticals, cosmetics, detergents, plastics, and lube oils and in textile manufacture. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed) Fatty Alcohol,Alcohol, Fatty,Alcohols, Fatty
D006139 Guaiacol An agent thought to have disinfectant properties and used as an expectorant. (From Martindale, The Extra Pharmacopoeia, 30th ed, p747) 2-Hydroxy-Anisole,2-Hydroxyanisole,2-Methoxy-Phenol,2-Methoxyphenol,Guaicol,Methyl Catechol,Catechol, Methyl
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D019440 Anti-Obesity Agents Agents that increase energy expenditure and weight loss by neural and metabolic regulation. Anti-Obesity Agent,Anti-Obesity Drug,Antiobesity Agent,Antiobesity Drug,Weight-Loss Agents,Weight-Loss Drug,Anti-Obesity Drugs,Antiobesity Agents,Antiobesity Drugs,Weight-Loss Drugs,Agent, Anti-Obesity,Agent, Antiobesity,Agents, Anti-Obesity,Agents, Antiobesity,Agents, Weight-Loss,Anti Obesity Agent,Anti Obesity Agents,Anti Obesity Drug,Anti Obesity Drugs,Drug, Anti-Obesity,Drug, Antiobesity,Drug, Weight-Loss,Drugs, Anti-Obesity,Drugs, Antiobesity,Drugs, Weight-Loss,Weight Loss Agents,Weight Loss Drug,Weight Loss Drugs

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