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.


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.


METHODS
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.
Roche Centre for Applied Clinical Development, Welwyn Garden City, UK.
Adam J
AJ
Foley-Comer
Anne-Marie
AM
Young
Fiona
F
Russell-Yarde
Paul
P
Jordan
D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D000069059:Atorvastatin; D018592:Cross-Over Studies; D004347:Drug Interactions; D005260:Female; D005464:Fluorobenzenes / Q000493:pharmacokinetics* / Q000494:pharmacology; D006538:Heptanoic Acids / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010080:Oxazoles / Q000493:pharmacokinetics* / Q000494:pharmacology; D047493:PPAR alpha / Q000819:agonists; D047495:PPAR gamma / Q000819:agonists; D011743:Pyrimidines / Q000493:pharmacokinetics* / Q000494:pharmacology; D011758:Pyrroles / Q000493:pharmacokinetics* / Q000494:pharmacology; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000493:pharmacokinetics* / Q000494:pharmacology; D013876:Thiophenes / Q000493:pharmacokinetics* / Q000494:pharmacology; D055815:Young Adult
D005464:Fluorobenzenes; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010080:Oxazoles; D047493:PPAR alpha; D047495:PPAR gamma; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D013876:Thiophenes; C542437:aleglitazar; D000068718:Rosuvastatin Calcium; D000069059:Atorvastatin