Pharmacokinetics of oltipraz in rat models of diabetes mellitus induced by alloxan or streptozotocin
| Autor: | Jin Wan Kim, Sihyung Yang, Taekrho Kim, Ji Young Kim, Myung Gull Lee, Soo K. Bae |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Male
medicine.medical_specialty Administration Oral Thiophenes Streptozocin General Biochemistry Genetics and Molecular Biology Diabetes Mellitus Experimental Rats Sprague-Dawley chemistry.chemical_compound Pharmacokinetics Oral administration Diabetes mellitus Internal medicine Alloxan Oltipraz Animals Medicine RNA Messenger General Pharmacology Toxicology and Pharmaceutics Chromatography High Pressure Liquid business.industry Thiones Half-life Blood Proteins General Medicine Streptozotocin medicine.disease Blood proteins Rats Endocrinology chemistry Pyrazines Injections Intravenous Microsomes Liver business Half-Life Protein Binding medicine.drug |
| Zdroj: | Life Sciences. 78:2287-2294 |
| ISSN: | 0024-3205 |
| DOI: | 10.1016/j.lfs.2005.09.031 |
| Popis: | Pharmacokinetic parameters of oltipraz were compared after intravenous (10 mg/kg) and oral (30 mg/kg) administration in rat model of diabetes mellitus induced by alloxan (rat model of DMIA) or streptozotocin (rat model of DMIS) and their respective control male Sprague-Dawley rats. In rat models of DMIA and DMIS, the expressions and mRNA levels of CYP1A2, 2B1/2, and 3A1(23) increased, and oltipraz was metabolized mainly via CYP1A1/2, 2B1/2, 2C11, 2D1, and 3A1/2 in male Sprague-Dawley rats. Hence, it would be expected that the AUC and CL values of oltipraz would be significantly smaller and faster, respectively, in rat models of diabetes. This was proven by the following results. After intravenous administration, the AUC values were significantly smaller in rat models of DMIA (40.1% decrease) and DMIS (26.0% decrease) than those in respective control rats, and this could be due to significantly faster CL values in rat models of DMIA (40.1% increase) and DMIS (26.0% increase). The faster CL could be due to increase in hepatic blood flow rate and significantly faster CL(int) in rat models of diabetes, since oltipraz is an intermediate hepatic extraction ratio drug in male Sprague-Dawley rats. After oral administration, the AUC values of oltipraz were also significantly smaller in rat models of DMIA (54.0% decrease) and DMIS (63.2% decrease). This could be due to increase in hepatic blood flow rate, significantly faster CL(int), and changes in the intestinal first-pass effect in rat models of diabetes. However, this was not due to decrease in absorption in rat models of diabetes. |
| Databáze: | OpenAIRE |
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