Aleglitazar, a balanced PPAR alpha/gamma agonist, has no clinically relevant pharmacokinetic interaction with high-dose atorvastatin or rosuvastatin

Background: Aleglitazar, a dual PPAR-alpha/gamma 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 mu g, 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.