Metabolic Fate of a New Anti-ulcer Drug (+)-(1R, 4aS, 10aR)-1,2,3,4,4a, 9,10,10a-Octahydro-1,4a-dimethyl-7-(1-methylethyl)-6-sulfo-1-phenanthrenecarboxylic Acid 6-Sodium Salt Pentahydrate (TA-2711). I. Disposition, Metabolism and Protein Binding in Rats a
スポンサーリンク
概要
- 論文の詳細を見る
Metabolic fate of (+)-(1R, 4aS, 10aR)-1,2,3,4,4a, 9,10,10a-octahydro-1,4a-dimethyl-7-(1-methylethyl)-6-sulfo-1-phenanthrenecarboxylic acid 6-sodium salt pentahydrate (TA-2711), a new anti-ulcer drug, was studied in animals using ^<14>C-TA-2711. The absorption was estimated to be 3.4-7.0% of dose in rats. The plasma radioactivity after oral dosing peaked at 5-6 h in rats and at 2 h in dogs, and their elimination half lives (β) were about 120-130 h. After oral or intravenous administration of TA-2711 to rats, the concentrations of radioactivity in most of the tissues were much lower than that in the plasma, indicating the low transfer of TA-2711 into the tissues from the plasma. In whole body autoradiograms of rats, most of the radioactivity given orally was localized in the gastrointestinal tract. Almost all the radioactivity given orally was excreted to the feces while the urinary excretion was extremely low. The sole and slight metabolite, glucuronide of TA-2711,was detected only in the urine of rats and dogs after oral dosing. During the consecutive oral dosing once a day for 21 d to rats, the plasma levels attained the steady state after administration of drug 7-10 more times. After the final dosing, the patterns of disappearance of radioactivity in the plasma were similar to those in the tissues, and the tissue/plasma ratios of the concentrations were similar to those after single dosing, suggesting no accumulation in rat tissues. More than 96% and about 85% of TA-2711 was bound in vitro to human and rat serum proteins, mainly albumin, respectively. No radioactivity was found in fetus and milk of rats given oral administration.
- 公益社団法人日本薬学会の論文
著者
-
Ito Yutaka
Biological Research Laboratory Tanabe Seiyaku Co. Ltd.
-
SUGAWARA Yoichi
Biological Research Laboratory, Tanabe Seiyaku Co. Ltd.
-
TAKAITI Osasi
Biological Research Laboratory, Tanabe Seiyaku Co. Ltd.
-
NAKAMURA Susumu
Biological Research Laboratory, Tanabe Seiyaku Co. Ltd.
-
FUKUSHIMA Takeshi
Biological Research Laboratory, Tanabe Seiyaku Co. Ltd.
-
Nakamura Susumu
Biological Research Laboratory Tanabe Seiyaku Co. Ltd.
-
Fukushima Takeshi
Department Of Bio-analytical Chemistry Graduate School Of Pharmaceutical Sciences Thc University Of
-
Fukushima Takeshi
Biological Research Laboratory Tanabe Seiyaku Co. Ltd.
-
Takaiti O
Tanabe Seiyaku Co. Ltd. Saitama Jpn
-
Sugawara Yoichi
Biological Research Laboratory Tanabe Seiyaku Co. Ltd.
関連論文
- Urinary Excretion of D-Serine in Human : Comparison of Different Ages and Species
- Metabolic Fate of a New Anti-ulcer Drug (+)-(1R, 4aS, 10aR)-1,2,3,4,4a, 9,10,10a-Octahydro-1,4a-dimethyl-7-(1-methylethyl)-6-sulfo-1-phenanthrenecarboxylic Acid 6-Sodium Salt Pentahydrate (TA-2711). II. Distribution in the Rat Stomach
- Metabolic Fate of a New Anti-ulcer Drug (+)-(1R, 4aS, 10aR)-1,2,3,4,4a, 9,10,10a-Octahydro-1,4a-dimethyl-7-(1-methylethyl)-6-sulfo-1-phenanthrenecarboxylic Acid 6-Sodium Salt Pentahydrate (TA-2711). I. Disposition, Metabolism and Protein Binding in Rats a
- Metabolism of Diltiazem. III. Oxidative Deamination of Diltiazem in Rat Liver Microsomes
- Metabolism of Diltiazem. II. Metabolic Profile in Rat, Dog and Man
- Metabolism of Diltiazem. I. Structures of New Acidic and Basic Metabolites in Rat, Dog and Man
- Age-Related Weakening of Baroreflex-Mediated Sympathetic Activity in Spontaneously Hypertensive Rats in Response to Blood Pressure Reduction
- Liquid chromatographic-atmospheric pressure chemical ionization mass spectrometric determination of anandamide and its analogs in rat brain and peripheral tissues
- Effect of Icaria Chemotactic Peptide and Its Analogue on the Intracellular Calcium Changes in Guinea Pig Neutrophils
- Optimization of the Reaction Conditions for the Peroxyoxalate Chemiluminescence Detection System of Fluorescent Compounds in a High-Performance Liquid Chromatography
- PHARMACOKINETIC STUDIES ON 1-(2-CHLOROETHYL)-3-ISOBUTYL-3-(β-MALTOSYL)-1-NITROSOUREA (TA-077). I. BLOOD AND TISSUE CONCENTRATIONS OF A NEW NITROSOUREA ANTITUMOR AGENT TA-077 AND ITS METABOLITE TA-G AFTER INTRAVENOUS INJECTION OF TA-077 IN VARIOUS EXPERIME
- Accumulation of Radioactivity in Rat Brain and Peripheral Tissues Including Salivary Gland after Intravenous Administration of 14C-D-aspartic Acid
- Metabolism of a New Orally Active Dopamine Prodrug, N-(N-Acetyl-L-methionyl)-O, O-bis(ethoxycarbonyl)dopamine (TA-870) and Dopamine after Oral Administration to Rats and Dogs
- GLUCOSE CONJUGATION : METABOLISM OF PANTOTHENIC ACID AND HOPANTENIC ACID
- Studies on the fate of D-aspartic acid in pineal and pituitary glands of rats after intravenous administration
- D-Serine Concentration in Blood Serum of Liver Transplanted Patients
- Enantiomeric Separation of NBD-Amino Acids by Capillary Zone Electrophoresis Using Cyclodextrins as Chiral Selectors