An open-label, randomized, three-way crossover trial of the effects of coadministration of rosuvastatin and fenofibrate on the pharmacokinetic properties of rosuvastatin and fenofibric acid in healthy male volunteers.
BACKGROUND
Rosuvastatin and fenofibrate are lipid-regulating agents with different modes of action. Patients with dyslipidemia who have not achieved treatment targets with monotherapy may benefit from the combination of these agents.


OBJECTIVE
The effect of coadministration of rosuvastatin and fenofibrate on the steady-state pharmacokinetics of rosuvastatin and fenofibric acid (the active metabolite of fenofibrate) was assessed in healthy volunteers.


METHODS
This was an open-label, randomized, 3-way crossover trial consisting of three 7-day treatment periods. Healthy male volunteers received one of the following treatment regimens in each period: rosuvastatin 10 mg orally once daily; fenofibrate 67 mg orally TID; and rosuvastatin + fenofibrate dosed as above. The steady-state pharmacokinetics of rosuvastatin and fenofibric acid, both as substrate and as interacting drug, were investigated on day 7 of dosing. Treatment effects were assessed by construction of 90% CIs around the ratios of the geometric least-square means for rosuvastatin + fenofibrate/rosuvastatin and rosuvastatin + fenofibrate/fenofibrate for the area under the plasma concentration-time curve (AUC) and maximum plasma concentration (derived from analysis of variance of log-transformed parameters).


RESULTS
Fourteen healthy male volunteers participated in the study. When rosuvastatin was coadministered with fenofibrate, there were minor increases in the AUC from 0 to 24 hours and maximum concentration (Cmax) of rosuvastatin: the respective geometric least-square means increased by 7% (90% CI, 1.00-1.15) and 21% (90% CI, 1.14-1.28). The pharmacokinetic parameters of fenofibric acid were similar when fenofibrate was dosed alone and with rosuvastatin: the geometric least-square means for fenofibric acid AUC from 0 to 8 hours and Cmax decreased by 4% (90% CI, 0.90-1.02) and 9% (90% CI, 0.84-1.00), respectively. The treatments were well tolerated alone and in combination.


CONCLUSIONS
Coadministration of rosuvastatin and fenofibrate produced minimal changes in rosuvastatin and fenofibric acid exposure.
AstraZeneca, Alderley Park, Macclesfield, Cheshire, United Kingdom. paul.martin@astrazeneca.com
Paul D
PD
Martin
Aaron L
AL
Dane
Dennis W
DW
Schneck
Michael J
MJ
Warwick
D000328:Adult; D019540:Area Under Curve; D018592:Cross-Over Studies; D004347:Drug Interactions; D011345:Fenofibrate / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics*; D005464:Fluorobenzenes / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000097:blood / Q000493:pharmacokinetics*; D000960:Hypolipidemic Agents / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides; D013997:Time Factors
D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; C006012:fenofibric acid; D011345:Fenofibrate