Simultaneous administration of fluoxetine and simvastatin ameliorates lipid profile, improves brain level of neurotransmitters, and increases bioavailability of simvastatin
| Autor: | Abdulrahman K. Al-Asmari, Zabih Ullah, Ishtiaque Ahmad, Aqeel Salman Al Masoudi |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
animal structures
Cmax Pharmacology neurotransmitters chemistry.chemical_compound Pharmacokinetics Medicine simvastatin Pharmacology (medical) Original Research drug interaction medicine.diagnostic_test Triglyceride business.industry Cholesterol fluoxetine Drug interaction Journal of Experimental Pharmacology chemistry Simvastatin Pharmacodynamics Molecular Medicine lipid levels business Lipid profile bioavailability medicine.drug |
| Zdroj: | Journal of Experimental Pharmacology |
| ISSN: | 1179-1454 |
| Popis: | Abdulrahman K Al-Asmari,1 Zabih Ullah,1 Aqeel Salman Al Masoudi,2 Ishtiaque Ahmad1 1Department of Research, Prince Sultan Military Medical City, Riyadh, 2Department of Research and Education, King Abdulaziz Airbase Armed Forces Hospital, Dhahran, Saudi Arabia Abstract: Simvastatin (STT), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, is widely prescribed for dyslipidemia, whereas fluoxetine (FLX) is the first-choice drug for the treatment of depression and anxiety. A recent report suggests that selective serotonin reuptake inhibitors can interact with the cytochrome P450 3A4 substrate, and another one suggests that STT enhances the antidepressant activity of FLX. However, the data are inconclusive. The present study was designed to explore the pharmacokinetic and pharmacodynamic consequences of coadministration of STT and FLX in experimental animals. For this, Wistar rats weighing 250±10g were divided into four groups, including control, STT (40mg/kg/day), FLX (20mg/kg/day), and STT+FLX group, respectively. After the dosing period of 4weeks, the animals were sacrificed, and the blood and brain samples were collected for the analysis of STT, simvastatin acid (STA), FLX, total cholesterol, triglyceride, high-density lipoprotein (HDL), 5-hydroxytryptamine, dopamine, and hydroxy indole acetic acid. It was found that the coadministration resulted in a significant increase in the bioavailability of STT in the plasma (41.8%) and brain (68.7%) compared to administration of STT alone (p |
| Databáze: | OpenAIRE |
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