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

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.