Effect of multidose cilostazol on pharmacokinetic and lipid profile of atorvastatin in male Wistar rats.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.
Pharmacy Department, BITS-Pilani Hyderabad Campus, Andhra Pradesh, India. rahulvats1983@gmail.com
Rahul
R
Vats
Kanthikiran V S
KV
Varanasi
Rambabu
R
Arla
Sridhar
S
Veeraraghavan
Shraddha
S
Rajak
Aditya Narasimha
AN
Murthy
D000818:Animals; D000069059:Atorvastatin; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D000077407:Cilostazol; D004347:Drug Interactions; D006538:Heptanoic Acids / Q000493:pharmacokinetics* / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D011758:Pyrroles / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D053719:Tandem Mass Spectrometry; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D013777:Tetrazoles; D014280:Triglycerides; D014665:Vasodilator Agents; D002784:Cholesterol; D000069059:Atorvastatin; D000077407:Cilostazol