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.
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