Effect of Colesevelam on Lovastatin Pharmacokinetics

Abstract

To assess potential interactions of colesevelam hydrochloride and lovastatin in healthy volunteers when lovastatin alone was administered with dinner, both lovastatin and colesevelam were administered with dinner, and colesevelam was administered with dinner and lovastatin was administered 4 hours later with a snack. A single-center, open-label, 3-period, crossover drug interaction study was performed with 22 healthy volunteers. Blood samples were collected at specified intervals before and after dosing, and plasma concentrations of lovastatin and lovastatin hydroxyacid were measured using a liquid chromatography/mass spectroscopy/mass spectroscopy method. Maximal concentration (Cmax), AUC from time 0 to the last time point measured (AUC0-t), and AUC0-infinity values for lovastatin were 102%, 94%, and 104%, and for lovastatin hydroxyacid were 102%, 91%, and 92%, respectively, of control values when colesevelam and lovastatin were coadministered with dinner. Administration of colesevelam with dinner and lovastatin 4 hours later with a snack resulted in a decreased Cmax and AUC0-t for lovastatin (63% and 37%, respectively; p < 0.05) and an increased Cmax and AUC0-t for lovastatin hydroxyacid (61% and 50%, respectively; p < 0.05), both compared with lovastatin alone administered with dinner. Colesevelam had no significant effect on lovastatin pharmacokinetics when coadministered with lovastatin at dinner. A split-dosing regimen resulted in alterations in pharmacokinetic parameters for lovastatin and lovastatin hydroxyacid that are likely due to known differences in the pharmacokinetics of lovastatin when administered to patients with meals or in a fasting state.