Pharmacokinetic interaction between ezetimibe and lovastatin in healthy volunteers.
BACKGROUND
Ezetimibe (Zetia) is a novel inhibitor of intestinal absorption of cholesterol that is approved for the treatment of primary hypercholesterolemia. In a separate pilot study, co-administration of ezetimibe and lovastatin resulted in a significant pharmacodynamic interaction, leading to an additive reduction in LDL-C. The current study was designed to further investigate the potential for pharmacokinetic interaction between ezetimibe and lovastatin.


METHODS
This was a randomized, open-label, 3-way crossover study in 18 healthy adult volunteers. All subjects received the following treatments orally once daily for 7 days: ezetimibe 10 mg, lovastatin 20 mg, or ezetimibe 10 mg plus lovastatin 20 mg. Plasma samples obtained on day 7 were evaluated for steady-state pharmacokinetics of ezetimibe (unconjugated), total ezetimibe (ezetimibe and ezetimibe-glucuronide conjugate), lovastatin, and beta-hydroxylovastatin.


RESULTS
Co-administration of ezetimibe with lovastatin did not affect the pharmacokinetics of ezetimibe. There were no significant differences in the exposure to total ezetimibe, ezetimibe-glucuronide and ezetimibe after co-administration with lovastatin vs. ezetimibe given alone. Co-administration of ezetimibe with lovastatin had no significant effect on the exposure to either lovastatin or beta-hydroxylovastatin. The point estimates based on the log-transformed Cmax and AUC values for lovastatin and beta-hydroxylovastatin were 113% and 119%, respectively, for co-administration of ezetimibe with lovastatin vs. lovastatin administration alone. Co-administration therapy with ezetimibe and lovastatin was safe and well tolerated.


CONCLUSIONS
Ezetimibe did not significantly affect the pharmacokinetics of lovastatin or beta-hydroxylovastatin and vice versa. Co-administration of ezetimibe and lovastatin is unlikely to cause a clinically significant pharmacokinetic drug interaction.
Reyderman
Larisa
L
Department of Drug Metabolism and Pharmacokinetics, Schering-Plough Research Institute, Kenilworth, NJ 07033-1300, USA. larisa.reyderman@spcorp.com
Kosoglou
Teddy
T
Boutros
Tanya
T
Seiberling
Michael
M
Statkevich
Paul
P
D000328:Adult; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001384:Azetidines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008148:Lovastatin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D012016:Reference Values
D000924:Anticholesteremic Agents; D001384:Azetidines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin; D000069438:Ezetimibe