Effect of multidose cilostazol on pharmacokinetic and lipid profile of atorvastatin in male Wistar rats
| Autor: | Shraddha Rajak, Aditya Narasimha Murthy, Rahul Vats, Kanthikiran Varanasi, Rambabu Arla, Sridhar Veeraraghavan |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Vasodilator Agents Atorvastatin Tetrazoles Pharmaceutical Science Blood lipids Pharmacology chemistry.chemical_compound Pharmacokinetics Tandem Mass Spectrometry medicine Animals Drug Interactions Pyrroles Rats Wistar Chromatography High Pressure Liquid Triglycerides medicine.diagnostic_test business.industry Cholesterol Cholesterol LDL Metabolism Cilostazol Rats chemistry Heptanoic Acids Microsomes Liver Microsome Hydroxymethylglutaryl-CoA Reductase Inhibitors Lipid profile business human activities medicine.drug |
| Zdroj: | Journal of Pharmacy and Pharmacology. 64:1638-1645 |
| ISSN: | 2042-7158 0022-3573 |
| DOI: | 10.1111/j.2042-7158.2012.01542.x |
| Popis: | Objectives Atorvastatin (ATV) and cilostazol (CLZ) are often co-prescribed to treat conditions such as peripheral arterial disease. In the present study, the drug–drug interaction potential of multi-dose CLZ on both pharmacokinetics and the lipid-lowering ability of single-dose ATV is demonstrated. Method The pharmacokinetic parameters of ATV were determined in Wistar rats after per-oral pre-treatment with CLZ for 7 days in order to assess the interaction potential between ATV and CLZ. In-vitro metabolic inhibition and everted gut sac studies were conducted to elucidate the mechanism of this interaction. Biochemistry analyser was used to estimate lipid profiles in Wistar rats. A validated LC-MS/MS method was employed to simultaneously quantify both ATV and CLZ in rat plasma matrix. Key findings A statistically significant increase in systemic exposure to ATV after a single dose was observed in CLZ pre-treated rats. In-vitro metabolism studies using rat liver microsome (RLM) demonstrated statistically significant inhibition of ATV metabolism when co-incubated with CLZ. No change in apparent permeability of ATV was observed in the presence of CLZ. The blood lipid profile study after ATV administration indicated a statistically significant decrease in total cholesterol, triglycerides and LDL-cholesterol. Conclusions Multi-dose administration of CLZ influences the pharmacokinetics and lipid-lowering properties of ATV. Collectively, an apparent interaction between selected drugs was evident. |
| Databáze: | OpenAIRE |
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