Aleglitazar, a balanced PPARα/γ agonist, has no clinically relevant pharmacokinetic interaction with high-dose atorvastatin or rosuvastatin

Abstract

Background: Aleglitazar, a dual PPAR-α/γ agonist, combines the lipid benefits of fibrates and the insulin-sensitizing benefits of thiazolidinediones.

Objective: To investigate the pharmacokinetic effects of co-administration of atorvastatin or rosuvastatin with aleglitazar.

Research design and methods: In a two-cohort, open-label, randomised, three-period crossover study, 44 healthy subjects received once-daily oral doses of aleglitazar 300 μg, statin (atorvastatin 80 mg or rosuvastatin 40 mg) and aleglitazar co-administered with each statin for 7 days. Plasma concentrations of each drug were measured and pharmacokinetic parameters determined on day 7 in each period.

Main outcome measures: Peak observed plasma concentration (C_max) and total exposures (AUC_{0 – 24}) of aleglitazar, atorvastatin and rosuvastatin.

Results: C_max and AUC_{0 – 24} to aleglitazar were similar, whether administered alone or in combination with a statin. Total exposure to either statin was unaffected by co-administration with aleglitazar. C_max treatment ratios for both statins exceeded the conventional no-effect boundary (1.25) when administered with aleglitazar.

Conclusions: Co-administration of aleglitazar with a statin does not alter the pharmacokinetic profile of either drug.

Keywords::

• cardiovascular pharmacology
• diabetes
• drug interactions
• pharmacokinetics
• statins

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