الفهرس 
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Abstract
Objective: The purpose of this study was to evaluate and compare the effects of multiple dose administration of atorvastatin or lovastatin on pharmacokinetics of aliskiren in rats with rationalization for the underlying possible mechanisms.
Materials and Methods:
A total of 90 healthy female Albino rats were randomly divided into 3 groups. All groups were dosed aliskiren by oral gavage at a dose of (8.57 mg /kg) daily for 14 days. group 1 (control group) received only water. group 2 (atorvastatin group) received, in addition to aliskiren, atorvastatin at a dose of (1.143 mg/kg) for seven days. group 3 (lovastatin group) received, in addition to aliskiren, lovastatin at a dose of (1.143 mg/kg) for seven days. After blood samples collection at specific times interval, aliskiren concentrations were determined using LC-MS/MS method.
Results:
Relative to the control, atorvastatin resulted in non-significant alterations in the pharmacokinetics parameters of aliskiren. In contrast, lovastatin resulted in a significant increase in AUC0–∞, Cmax and t1/2 by 21 % 10 %, and 72%, respectively. Additionally, lovastatin significantly reduced the CL/ F by 23%. The interaction was mild and resulted in no reported adverse effects.
Conclusion:
Only lovastatin causes a prominent increase in aliskiren bioavailability. Proposed mechanism is the inhibition of aliskiren metabolism via the hepatic CYP3A subfamily and/or inhibition of intestinal P-gp and/or the CYP3A subfamily. Caution should be taken when lovastatin and aliskiren are concomitantly administration in clinical practice.
Keywords: Aliskiren; Atorvastatin; Lovastatin; Drug interactions