| Autor: |
Saburo Sugai, Shiro Kondo, Toshio Tanaka, Isao Watanabe, Ryuji Tamaya, Toshio Suwa, Junji Shimazaki, Koichi Mitsugi, Yoshiro Kohno, Toshiya Minagawa, Kenji Manabe, Yoshio Esumi |
| Rok vydání: |
1995 |
| Předmět: |
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| Zdroj: |
Drug Metabolism and Pharmacokinetics. 10:344-358 |
| ISSN: |
0916-1139 |
| Popis: |
Blood levels, excretion and metabolism of 3H labeled isocarbacyclin methyl ester given in the form of an oil-in-water emulsion (3H-TTC-909) were compared with those after administration of the saline solution form (3H-TEI-9090) in the dog.1. After rapid intravenous injection of 3H-TTC-909, the blood level of radioactivity decreased tri-phasically, while a plateau level was established between 7 min and 1 hr after 3H-TEI-9090 dosing. The ratio of AUC values of unchanged drug and isocarbacyclin (TEI-7165) to those of total redioactivity after administration of 3H-TTC-909 were slightly higher than the values obtained after 3H-TEI-9090 dosing. Similar results were observed in the case of constant rate infusion for 1 hr of 3H-TTC-909 and 3H-TEI-9090.2. Radioactivity was excreted predominantly in urine and accounted for 78.3% and 70.4% within 7 days after dosing of 3H-TTC-909 and 3H-TEI-9090, respectively.3. The 13, 14-dihydro-15-oxo form of the unchanged drug (M-2), which was not previously detected in rat blood, existed in the blood samples immediately after intravenous rapid injection of 3H-TTC-909 and 3H-TEI-9090 in dogs. After hydrolysis of TEI-9090 and M-2, TEI-7165 and its 13, 14-dihydro-15-oxo form (M-4) were widely metabolized in a variety of pathways in dogs, as in the case of rats.4. Furthermote, two types of undefined conjugates (the ester-form conjugate and an amino acid conjugate) were postulated in the urine samples after administration of 3H-TTC-909. No significant differences in the composition of urinary metabolites was observed between 3H-TTC-909 and 3H-TEI-9090 dosing. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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