Pharmacokinetics of the new antihypertensive agent nipradilol in rats. 1st communication: Metabolism and disposition after single oral administration of [14C]nipradilol. 1985

S Kabuto, and H Kimata, and M Yonemitsu, and T Koide, and H Nakao, and J Suzuki

The metabolism and disposition of a new antihypertensive and antianginal agent, 3,4-dihydro-8-(2-hydroxy-3-isopropylamino)propoxy- 3-nitroxy-2H-1-benzopyran (nipradilol, K-351) were studied using its [14C]-labelled compound in rats. The plasma level of radioactivity reached the maximum 1 h after oral administration, and the majority of radioactivities administered were recovered in urine and via the bile in feces within 48 h. From the foregoing it is obvious that the drug was absorbed from the gastrointestinal tract rapidly and well, and was eliminated from the body completely. The unchanged drug detected in the plasma and urine after oral administration of 30 mg/kg was more than 10 times as much as that after 3 mg/kg. This fact indicates that the first-pass metabolism of the drug has been saturated. Denitronipradilol, 4- and 5-hydroxynipradilol, and 4- and 5-hydroxydenitronipradilol were identified as major metabolites in the plasma and excreta, and the degradation compounds of the aminohydroxypropoxy side chain were also found as minor metabolites. Among these metabolites, 4-hydroxy metabolites were found mainly as unconjugates and 5-hydroxy metabolites as glucuronides, respectively. These findings suggest that the possible metabolic pathways of nipradilol in rats involve reductive denitration of the nitroxy group, hydroxylation at the benzopyran skeleton, oxidative degradation of the beta-blocking side chain and their glucuronidation.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008297 Male Males
D011412 Propanolamines AMINO ALCOHOLS containing the propanolamine (NH2CH2CHOHCH2) group and its derivatives. Aminopropanols
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D002245 Carbon Dioxide A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. Carbonic Anhydride,Anhydride, Carbonic,Dioxide, Carbon
D002621 Chemistry A basic science concerned with the composition, structure, and properties of matter; and the reactions that occur between substances and the associated energy exchange.
D002855 Chromatography, Thin Layer Chromatography on thin layers of adsorbents rather than in columns. The adsorbent can be alumina, silica gel, silicates, charcoals, or cellulose. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Chromatography, Thin-Layer,Thin Layer Chromatography,Chromatographies, Thin Layer,Chromatographies, Thin-Layer,Thin Layer Chromatographies,Thin-Layer Chromatographies,Thin-Layer Chromatography
D005243 Feces Excrement from the INTESTINES, containing unabsorbed solids, waste products, secretions, and BACTERIA of the DIGESTIVE SYSTEM.
D005965 Glucuronates Derivatives of GLUCURONIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include the 6-carboxy glucose structure. Glucosiduronates,Glucuronic Acids,Acids, Glucuronic
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations

Related Publications

S Kabuto, and H Kimata, and M Yonemitsu, and T Koide, and H Nakao, and J Suzuki
January 1985, Drug metabolism and disposition: the biological fate of chemicals,
S Kabuto, and H Kimata, and M Yonemitsu, and T Koide, and H Nakao, and J Suzuki
January 1991, Drug metabolism and disposition: the biological fate of chemicals,
S Kabuto, and H Kimata, and M Yonemitsu, and T Koide, and H Nakao, and J Suzuki
January 1992, Drug metabolism and disposition: the biological fate of chemicals,
S Kabuto, and H Kimata, and M Yonemitsu, and T Koide, and H Nakao, and J Suzuki
January 2017, Drug metabolism letters,
S Kabuto, and H Kimata, and M Yonemitsu, and T Koide, and H Nakao, and J Suzuki
May 2011, Drug metabolism and disposition: the biological fate of chemicals,
S Kabuto, and H Kimata, and M Yonemitsu, and T Koide, and H Nakao, and J Suzuki
July 2010, Drug metabolism and disposition: the biological fate of chemicals,
S Kabuto, and H Kimata, and M Yonemitsu, and T Koide, and H Nakao, and J Suzuki
July 1987, Arzneimittel-Forschung,
Copied contents to your clipboard!